text: as it is described above , the cyano compound of formula ( iii ) as free base or as a salt thereof is obtained from the sulfonate of formula ( iv ). preferably , the compound of formula ( iii ) is obtained as free base from the compound of formula ( iv ). the conversion is carried out by reaction of the compound ( iv ) with an alkaline metal cyanide such as sodium or potassium cyanide , in an appropriate solvent such as dimethylformamide , dimethylsulfoxide , ethyl acetate or acetonitrile , and at a temperature comprised between 0 ° c . and reflux temperature . preferably , the reaction is carried out at about 60 ° c . the reaction can be carried out in the presence of a phase transfer catalyst . example of suitable phase transfer catalysts are tri - c 8 - 10 - alkylmethylammonium chlorides , tetrabutylammonium bromide , hexadeciltrimethylammonium chloride , methyltrioctilammonium chloride , tetrabutylammonium chloride or tetrabutylammonium hydrogen sulfate . in a preferred embodiment the tetrabutylammonium hydrogen sulfate is used as phase transfer catalyst . in the present invention , preferred sulfonate compounds of formula ( iv ) are those where the sulfonate ( iv ) is a mesylate ( r 1 = methyl ), a besylate ( r 1 = phenyl ) or a tosylate ( r 1 = 4 - methylphenyl ). the most preferred sulfonate ( iv ) is the mesylate . the compound of formula ( iii ) can be converted into its salts , and its salts can be converted into the free compound by methods known in the art . the amide compound of formula ( ii ) can be prepared from the cyano compound of formula ( iii ) as free base or as a salt by hydrolysis . preferably , the compound of formula ( ii ) is obtained from the compound of formula ( iii ) as free base . for instance , hydrolysis can be achieved using mild conditions and / or by shortening the reaction time . the conditions to carry out the hydrolysis may be easily determined by the person skilled in the art by routine tests . for example , the hydrolysis can be carried out using the same reacting conditions for carrying out the hydrolysis of the cyano compound to montelukast but reducing the reaction time , as it illustrated in example 9 , followed by the isolation of the amide compound ( ii ). the last step of the process is a hydrolysis reaction . the compound of formula ( ii ) can be hydrolyzed to afford montelukast . the hydrolysis reaction can also be directly performed from the cyano compound ( iii ) as free base or as a salt to afford montelukast . preferably , the hydrolysis of the compound of formula ( ii ) or of the compound of formula ( iii ) as free base or as a salt is carried out with a base . preferably the base is an alkaline metal hydroxide or an alkaline earth metal hydroxide . more preferably , the base is sodium hydroxide , potassium hydroxide or lithium hydroxide . the most preferred one is sodium hydroxide . the reaction can be carried out in different solvent systems . preferably the solvent system is a solvent mixture comprising c 1 - c 4 alcohol and water . preferably the c 1 - c 4 alcohol is ethanol or isopropanol . the most preferred one is ethanol . typically , the hydrolysis of the cyano compound ( iii ) to montelukast ( i ) is carried out at reflux temperature and it is essentially complete within 24 hours . other suitable solvent system can be a two - phase solvent mixture comprising water and a suitable organic solvent non - miscible in water or sparingly miscible in water , optionally in the presence of a phase transfer catalyst . preferably the organic solvent is a ( c 6 - c 8 )- aromatic hydrocarbon . the most preferred one is toluene . suitable phase transfer catalyst include for instance , an ammonium quaternarium salt such as tetrabutylammonium bromide , tri - c 8 - c 10 - alkylmethylammonium chlorides , methyltrioctilammonium chloride or hexadeciltrimethylammonium chloride . the hydrolysis can be carried out at a temperature comprised between room temperature and reflux temperature . typically , in these reaction conditions the hydrolysis of the cyano compound ( iii ) to montelukast ( i ) is carried out at 120 ° c . and it is essentially complete within about seven days . the isolation of crude montelukast can be accomplished by diluting the crude with toluene and washing the solution with aqueous acetic acid and subsequently with water at room temperature , followed by evaporation of the solvent . the obtained montelukast can be purified by several methods , for instance , by aqueous acid - base extractions or by recrystallization . montelukast free acid obtained by the process of the present invention may be converted into pharmaceutically acceptable salts , and salts may be converted into free acid compounds , by known methods described in the art . it is also possible to isolate a salt of montelukast from the hydrolysis reaction , i . e . without isolating the montelukast free acid . the sulfonate compounds of formula ( iv ) are prepared from the alcohol of formula ( v ) by reaction with the corresponding sulfonyl chloride . this reaction is carried out in an appropriate solvent and in the presence of a tertiary amine , at a temperature comprised between − 20 ° c . and room temperature . preferably , the reaction is carried out at low temperatures . common solvents for the reaction include chlorine - containing solvents such as methylene chloride or 1 , 2 - dichloroethylene , aromatic hydrocarbons such as toluene or xylene , and dimethylformamide . examples of suitable tertiary amines are diisopropylethylamine and triethylamine . the preparation of the alcohol of formula ( v ) as free base or as a salt from the compound of formula ( vi ) is carried out by reaction with a methyl magnesium halide such as methyl magnesium chloride or methyl magnesium bromide , optionally in the presence of cerium chloride , or by reaction with methyl lithium , in the presence of a suitable solvent . examples of suitable solvents include an ether such as tetrahydrofurane , or an aromatic hydrocarbon such as toluene or xylene , or mixtures of them . preferably the reaction is carried out at a temperature comprised between − 78 ° c . and 20 ° c ., more preferably , at − 20 ° c . the alcohol of formula ( v ) can be converted into its salts , and its salts can be converted into the free compound by methods known in the art . for instance , the citrate salt is prepared by reaction of the compound of formula ( v ) as free base with citric acid in the presence of a suitable solvent . the compound of formula ( vi ) as free base or as a salt can be prepared from the known compound of formula ( vii ), which is reacted with the compound of formula ( viii ) in a suitable solvent such as dimethylformamide , dimethylsulfoxide , dichloromethane , toluene or tetrahydrofurane , and in the presence of a base such as cesium carbonate , sodium hydroxide and lithium bis ( trimethylsilyl ) amide . preferably , the reaction is carried out at a temperature comprised between − 10 ° c . and 60 ° c ., more preferably , at a 0 - 5 ° c . the compound of formula ( vi ) can be converted into its salts , and its salts can be converted into the free compound by methods known in the art . for instance , the oxalate salt is prepared by reaction of the compound of formula ( vi ) as free base with oxalic acid in the presence of a suitable solvent . the compound of formula ( vii ) may be prepared according to a known process described in us 2005107612 . the process described in this document comprises the reaction of the methyl - 2 -(( s )- 3 -( 3 -(( e )- 2 -( 7 - chloroquinolin - 2 - yl ) vinyl ) phenyl )- 3 - hydroxypropyl ) benzoate of formula ( ix ) with methane sulfonyl chloride or toluene sulfonyl chloride to form the methyl - 2 -(( s )- 3 -( 3 -( e )-( 2 -( 7 - chloroquinolin - 2 - yl ) vinyl ) phenyl )- 3 -[( methylsulfonyl ) oxy ] propyl ) benzoate or the corresponding tosylate . analogously , the besylate of formula ( vii ) can be obtained from the corresponding benzene sulfonyl chloride . the compound of formula ( viii ) can be prepared from 5 , 7 - dioxa - 6 - thiaspiro [ 2 . 5 ] octane 6 - oxide according to the process summarized in scheme 1 . the preparation process of the compound of formula ( viii ) involves the reaction of the compound of formula ( xi ) with potassium ethanethioate to give the compound of formula ( x ). typically , such reaction is carried out with an excess of potassium ethanethiolate in an appropriate solvent . examples of suitable solvents include dimethylsulfoxide , dimethylformamide , ethyl acetate , acetonitrile or mixtures thereof . preferably the reaction is carried out at a temperature comprised between room temperature and 70 ° c . after the isolation of the compound of formula ( x ), it can be hydrolyzed using an acid or a basic catalyst to give the compound of formula ( viii ). examples of suitable acids are hydrochloric acid , sulfuric acid , acetic acid and formic acid . examples of suitable bases are hydroxides , carbonates and alcoxide of an alkaline or an earth alkaline metal . example of suitable solvents are ( c 1 - c 6 )- alcohols , ( c 6 - c 8 )- aromatic hydrocarbons , dimethylformamide , dimethylsulfoxide , or mixtures of them . the best conditions to carry out the process of the present invention vary according to the parameters considered by a person skilled in the art , such as the starting materials , molar ratio , temperature , and similar . such reaction conditions may be easily determined by a person skilled in the art by routine tests , and with the teaching of the examples included in this document . throughout the description and claims the word “ comprise ” and variations of the word , are not intended to exclude other technical features , additives , components , or steps . the abstract of this application is incorporated herein as reference . additional objects , advantages and features of the invention will become apparent to those skilled in the art upon examination of the description or may be learned by practice of the invention . the following examples are provided by way of illustration , and they are not intended to be limiting of the present invention . 200 g of 5 , 7 - dioxa - 6 - thiaspiro [ 2 . 5 ] octane 6 - oxide were dissolved in 1 . 2 l of dimethyl sulfoxide and 308 g of potassium ethanethioate were poured to the solution . then , the suspension was heated at 40 ° c . for 5 . once the reaction was completed , a combination of 3 . 6 l of ethyl acetate and 3 . 61 of water was added . the organic phase was separated , washed with water and concentrated to dryness . 200 g of s -( 1 -( hydroxymethyl ) cyclopropyl ) methyl ethanethioate were recovered . yield : 78 % corrected by gc . 1 h nmr ( 400 mhz , cdcl 3 ): 3 . 45 ( 2h , d , j : 6 . 4 hz ); 3 . 01 ( 2h , s ); 2 . 53 ( oh , broad triplet , j : 6 . 4 hz ); 2 . 39 ( 3h , s ); 0 . 54 ( 4h , m ). 200 g of s -( 1 -( hydroxymethyl ) cyclopropyl ) methyl ethanethioate were dissolved in 2 l of methanol . then , 111 ml of concentrated hcl were added under a nitrogen blanket and the solution was stirred at room temperature for 10 . the solvent was distilled off and the residue was re - dissolved in 1 . 5 l of dimethylformamide to be used in the preparation of methyl 2 -(( r )- 3 -( 3 -(( e )- 2 -( 7 - chloroquinolin - 2 - yl ) vinyl ) phenyl )- 3 -((( 1 -( hydroxymethyl ) cyclopropyl ) methyl ) sulfanyl ) propyl ) benzoate . yield : 100 %. 1 h nmr ( 400 mhz , cdcl 3 ): 3 . 57 ( 2h , s ); 2 . 63 ( 2h , d , j : 8 . 0 hz ); 2 . 45 ( oh , broad signal ,); 1 . 43 ( 5h , t , j : 8 . 0 hz ); 0 . 52 ( 4h , m ). preparation of methyl 2 -(( s )- 3 -( 3 -(( e )- 2 -( 7 - chloroquinolin - 2 - yl ) vinyl ) phenyl )- 3 -[( methylsulfonyl ) oxy ] propyl ) benzoate ( vii with r 2 : ch 3 ) 12 . 1 ml de diisopropylethylamine were poured to a stirred solution of 24 . 5 g of methyl 2 -(( s )- 3 -( 3 -(( e )- 2 -( 7 - chloroquinolin - 2 - yl ) vinyl ) phenyl )- 3 - hydroxypropyl ) benzoate in 120 ml of dichloromethane . the mixture is cooled to − 20 ° c . and 5 ml of mesyl chloride were added slowly . once the reaction was completed , the crude solution was successively washed with 120 ml of an aqueous 10 % nahco 3 solution and 120 ml of water . finally , the solvent was distilled off to obtain 29 g of the title compound . the product was re - dissolved in 290 ml of dimethylformamide to be used as a solution in the next step . yield : 100 %. a solution of 19 g of ( 1 -( mercaptomethyl ) cyclopropyl ) methanol in 190 ml of dimethylformamide was cooled to 0 ° c . then , 52 g of cs 2 co 3 were added in one portion . after 10 min , the outcome solution from the previous example was added and the suspension was maintained at the same temperature for 18 hours . finally , a mix of 380 ml of ethyl acetate and 380 ml of water was poured to the solution crude . the organic phase was washed with 380 ml of water and concentrated to dryness . 30 g of brown oil were recovered . yield : 86 %, corrected after hplc analysis . 1 h nmr ( 400 mhz , dmso - d 6 ): 8 . 38 ( 1h , d , j : 8 . 4 hz ); 8 . 00 - 7 . 26 ( 14h , m ); 4 . 50 ( oh , t , j : 5 . 4 hz ); 3 . 92 ( 1h , t , 7 . 2 hz ); 3 . 76 ( 3h , s ); 3 . 33 ( 1h , dd , j : 11 . 0 hz , 5 . 4 hz ); 3 . 25 ( 1h , dd , j : 11 . 0 hz , 5 . 4 hz ); 2 . 98 - 2 . 88 ( 1h , m ); 2 . 83 - 2 . 74 ( 1h , m ); 2 . 52 ( 1h , d , j : 12 . 7 hz ); 2 . 39 ( 1h , d , j : 12 . 7 hz ); 2 . 10 ( 2h , m ); 0 . 46 - 0 . 18 ( 4h , m ). the product obtained in the previous example was dissolved in 300 ml of tetrahydrofuran . the mixture was cooled to 0 ° c . and 307 ml of 1 . 4m solution of methylmagnesium bromide were added under a nitrogen blanket . the reaction was maintained at 0 ° c . for 18 hours . then , 400 ml of 2m aqueous solution of acetic acid were added slowly , followed of 400 ml of ethyl acetate . the organic phase was successively washed with 400 ml of an aqueous 10 % nahco 3 solution and 400 ml of water . finally , the solvent was distilled off to yield 30 g of crude . yield : 81 % corrected after hplc analysis . 1 h nmr ( 400 mhz , dmso - d 6 ): 8 . 39 ( 1h , d , j : 8 . 6 hz ); 8 . 00 - 7 . 06 ( 14h , m ); 4 . 91 ( oh , s ); 4 . 51 ( oh , t , j : 5 . 5 hz ); 3 . 99 ( 1h , t , 7 . 3 hz ); 3 . 34 ( 1h , dd , j : 11 . 0 hz , 5 . 5 hz ); 3 . 26 ( 1h , dd , j : 11 . 0 hz , 5 . 5 hz ); 3 . 05 ( 1h , m ); 2 . 74 ( 1h , m ); 2 . 54 ( 1h , d , j : 12 . 7 hz ); 2 . 41 ( 1h , d , j : 12 . 7 hz ); 2 . 15 ( 2h , m ); 1 . 44 ( 6h , s ); 0 . 45 - 0 . 36 ( 2h , m ); 0 . 33 - 0 . 22 ( 2h , m ). 1 . 3 g of anhydrous cerium chloride were stirred in 10 ml of dry tetrahydrofuran for 18 hours at room temperature . then , the suspension was cooled to − 20 ° c . and 1 . 5 ml of a 3m solution of methylmagnesium chloride were added under a nitrogen blanket . after a period of time , a 2 . 5 ml tetrahydrofuran solution of 0 . 5 g of the product obtained in example 4 was added . the mixture was stirred for 18 hours at the same temperature and 10 ml of 2m aqueous solution of acetic acid were added slowly , followed of 10 ml of ethyl acetate . the organic phase was successively washed with 10 ml of an aqueous 10 % nahco 3 solution and 10 ml of water . finally , the solvent was distilled off to yield 0 . 5 g of crude . yield : 80 % corrected after hplc analysis . preparation of ( r , e )-( 1 -(( 1 -( 3 -( 2 -( 7 - chloroquinolin - 2 - yl ) vinyl ) phenyl )- 3 -( 2 -( 2 - hydroxypropan - 2 - yl ) phenyl ) propyl ) sulfanyl ) methyl ) cyclopropyl ) methyl methanesulfonate (( iv ) with r 1 ═ ch 3 ) 6 . 5 ml de diisopropylethylamine were poured to a stirred solution of 16 g of 2 -( 2 -(( r )- 3 -( 3 -(( e )- 2 -( 7 - chloroquinolin - 2 - yl ) vinyl ) phenyl )- 3 -((( 1 -( hydroxymethyl ) cyclopropyl ) methyl ) sulfanyl ) propyl ) phenyl ) propan - 2 - ol in 160 ml of dichloromethane . the mixture was cooled to − 20 ° c . and 2 . 7 ml of mesyl chloride were added slowly . the mixture was stirred at the same temperature for one hour and then , it was washed twice with 300 ml of water . the solvent was distilled off and 18 g of crude were recovered . yield : 100 %. 1 h nmr ( 400 mhz , dmso - d6 ): 8 . 41 ( 1h , d , j : 9 . 6 hz ); 8 . 02 - 7 . 03 ( 14h , m ); 4 . 91 ( oh , s ); 4 . 12 ( 2h , m ); 4 . 02 ( 1h , t , j : 7 . 1 hz ); 3 . 12 ( 3h , s ); 3 . 09 - 3 . 02 ( 1h , m ); 2 . 78 - 2 . 71 ( 1h , m ); 2 . 54 ( 1h , d , j : 13 . 2 hz ); 2 . 46 ( 1h , d , j : 13 . 2 hz ); 2 . 15 ( 2h , m ); 1 . 43 ( 3h , s ); 1 . 42 ( 3h , s ); 0 . 68 - 0 . 45 ( 4h , m ). the crude obtained in the previous example was dissolved in 180 ml of dimethylformamide and 2 . 1 g of sodium cyanide were added in one portion to the solution . after 18 hours of stirring at 60 ° c ., 270 ml of ethyl acetate was poured into the mixture previously warmed to room temperature . then , two washes with 270 ml of water were carried out and the solvent was distilled off to afford 14 g of crude . yield : 75 % corrected after hplc analysis . 1 h nmr ( 400 mhz , dmso - d 6 ): 8 . 39 ( 1h , d , j : 8 . 6 hz ); 8 . 00 - 7 . 05 ( 14h , m ); 4 . 90 ( oh , s ); 4 . 04 ( 1h , t , j : 7 . 2 hz ); 3 . 06 ( 1h , m ); 2 . 76 ( 1h , m ); 2 . 67 ( 1h , m ); 2 . 33 ( 1h , m ); 2 . 30 ( 2h , s ); 2 . 13 ( 2h , m ); 1 . 43 ( 6h , s ); 0 . 59 - 0 . 43 ( 4h , m ). 1 . 8 g of crude obtained in example 8 were dissolved in 3 . 6 ml of toluene . then , 3 . 6 ml of water was added followed of 14 . 7 g of sodium hydroxide and 0 . 44 g of tetrabutylammonium bromide . the mixture was stirred at 120 ° c . for 30 hours . after this period of time , 10 ml of toluene and 10 ml of water were added to the reaction solution previously cooled to room temperature . the organic phase was separated and washed with 10 ml of water . finally , the solvent was distilled off and the crude was purified by standard methods in order to recover 77 mg of the title compound . yield : 6 %. 1 h nmr ( 400 mhz , dmso - d 6 ): 8 . 41 ( 1h , d , j : 8 . 6 hz ); 8 . 03 - 7 . 07 ( 15h , m ); 6 . 74 ( 1h , s ); 4 . 91 ( oh , s ); 4 . 02 ( 1h , t , j : 7 . 3 hz ); 3 . 04 ( 1h , m ); 2 . 75 ( 1h , m ); 2 . 57 ( 1h , d , j : 13 . 3 hz ); 2 . 45 ( 1h , d , j : 13 . 3 hz ); 2 . 16 ( 4h , m ); 1 . 43 ( 6h , s ); 0 . 50 - 0 . 27 ( 4h , m ). 5 . 2 g of crude obtained in example 8 were dissolved in 10 ml of toluene . then , 10 ml of water was added followed of 14 . 7 g of sodium hydroxide and 0 . 44 g of tetrabutylammonium bromide . the mixture was stirred at 120 ° c . for 7 days . after this period of time , 10 ml of toluene and 10 ml of water were added to the reaction solution previously cooled to room temperature . the organic phase was separated and successively washed with 10 ml of acetic acid and 10 ml of water . finally , the solvent was distilled off to recover 4 . 6 g of product , that can be purified by standard methods if it is necessary . yield : 83 %. 1 h nmr ( 400 mhz , dmso - d 6 ): 12 . 02 ( 1h , s ); 8 . 39 ( 1h , d , j : 8 . 6 hz ); 8 . 01 - 7 . 04 ( 14h , m ); 4 . 90 ( oh , s ); 4 . 00 ( 1h , t , j : 7 . 3 hz ); 3 . 05 ( 1h , m ); 2 . 76 ( 1h , m ); 2 . 56 ( 1h , d , j : 12 . 9 hz ); 2 . 47 ( 1h , d , j : 12 . 9 hz ); 2 . 32 ( 2h , s ); 2 . 16 ( 2h , m ); 1 . 44 ( 6h , s ); 0 . 52 - 0 . 33 ( 4h , m ). ir ( kbr )= 3573 . 1 , 3436 . 9 , 2919 . 2 , 1716 . 9 , 1608 . 9 , 1499 . 9 , 1408 . 8 , 1315 . 7 , 1223 . 9 , 1201 . 6 , 1173 . 0 , 1148 . 0 , 1134 . 9 , 1074 . 8 , 965 . 9 , 950 . 8 , 933 . 2 , 863 . 6 , 842 . 7 , 766 . 0 cm − 1 . 1 . 05 g of sodium hydroxide were poured to a solution of 1 g of ( r , e )- 2 -( 1 -(( 1 -( 3 -( 2 -( 7 - chloroquinolin - 2 - yl ) vinyl ) phenyl )- 3 -( 2 -( 2 - hydroxypropan - 2 - yl ) phenyl ) propyl ) sulfanyl ) methyl ) cyclopropyl ) acetonitrile in 5 ml of a mixture of ethanol : water ( 96 : 4 , v / v ). the outcome suspension was stirred at reflux temperature for 15 hours . after this period of time , the reaction mixture was cooled down to room temperature and diluted with 10 ml of toluene . then , 20 ml of a 2m aqueous solution of acetic acid were added slowly and the organic layer was separated and washed twice with 10 ml of water . finally , the solvent was distilled off to recover 0 . 9 g of product that can be purified by standard methods if it is necessary . yield : 91 %. 2 . 6 g of montelukast free acid were dissolved in 26 ml of toluene and 8 . 9 ml of 0 . 5m naoh solution in methanol were added slowly at room temperature . the mixture was stirred for 1 hour and the solvent was removed under vacuum to obtain a residue . then , heptane ( 24 ml ) was added over 30 min to a well stirred solution of the residue in 4 ml of ethyl acetate at room temperature . two hours after the addition , an off white solid was filtered off under a nitrogen atmosphere and washed with 5 ml of heptane . the wet product was dried under vacuum at 70 - 80 ° c . for 2 days to yield 2 . 7 g of amorphous solid form of montelukast sodium . yield : 100 %. 1 h nmr ( 400 mhz , dmso - d 6 ): 8 . 38 ( 1h , d , j : 8 . 6 hz ); 8 . 02 - 7 . 04 ( 14h , m ); 5 . 19 ( oh , s ); 4 . 01 ( 1h , t , j : 7 . 2 hz ); 3 . 08 ( 1h , m ); 2 . 72 ( 1h , m ); 2 . 69 ( 1h , d , j : 12 . 4 hz ); 2 . 54 ( 1h , d , j : 12 . 4 hz ); 2 . 22 ( 1h , m ); 2 . 10 ( 1h , d , j : 14 . 2 hz ); 2 . 10 ( 1h , m ); 1 . 96 ( 1h , d , j : 14 . 2 hz ); 1 . 45 ( 3h , s ); 1 . 44 ( 3h , s ); 0 . 46 - 0 . 32 ( 2h , m ); 0 . 28 - 0 . 15 ( 2h , m ). to a solution of 338 g ( 0 . 61 mol ) of methyl 2 -(( r )- 3 -( 3 -(( e )- 2 -( 7 - chloroquinolin - 2 - yl ) vinyl ) phenyl )- 3 -((( 1 -( hydroxymethyl ) cyclopropyl ) methyl ) sulfanyl ) propyl ) benzoate in 2 . 0 l of toluene a solution of 75 g ( 0 . 60 mol ) of oxalic acid dihydrate in 1 . 0 l of acetonitrile was slowly added at room temperature . the outcome suspension was stirred at room temperature during ten hours . the solid was filtered off and washed several times with toluene / acetonitrile 2 / 1 ( v / v ) mixture . the wet solid was dried under vacuum at 25 ° c . 304 g of a yellow solid were obtained . yield 78 %. dsc : 121 . 6 ° c . ( peak ). 1 h nmr ( 400 mhz , dmso - d6 ): 8 . 42 ( 1h , d , j : 8 . 6 hz ); 8 . 00 - 7 . 28 ( 14h , m ); 3 . 92 ( 1h , t , 7 . 3 hz ); 3 . 76 ( 3h , s ); 3 . 31 ( 1h , d , j : 11 . 0 hz ); 3 . 25 ( 1h , d , j : 11 . 0 hz ); 2 . 98 - 2 . 90 ( 1h , m ); 2 . 82 - 2 . 75 ( 1h , m ); 2 . 52 ( 1h , d , j : 12 . 7 hz ); 2 . 39 ( 1h , d , j : 12 . 7 hz ); 2 . 14 - 2 . 08 ( 2h , m ); 0 . 43 - 0 . 19 ( 4h , m ). dsc measurement was carried out in a perforated pan at a scan rate of 5 ° c ./ minute from 25 . 0 ° c . to 150 . 0 ° c . with a dsc mettler toledo dsc822 . 283 g of the oxalate salt prepared in example 13 were suspended in 1 . 7 l of toluene and 1 . 7 l of water . 35 % of aqueous hydrochloric acid solution was slowly added to the previous mixture until ph 6 . 5 was obtained . the organic phase was separated and washed with water . finally the solvent was distilled off under vacuum . 243 g of an oil was obtained . yield 100 %. a solution of 92 . 5 g of 2 -( 2 -(( r )- 3 -( 3 -(( e )- 2 -( 7 - chloroquinolin - 2 - yl ) vinyl ) phenyl )- 3 -((( 1 -( hydroxymethyl ) cyclopropyl ) methyl ) sulfanyl ) propyl ) phenyl ) propan - 2 - ol ( hplc : 78 area %) in 910 ml of toluene was heated to 55 ° c . then , 34 . 8 g of citric acid monohydrate were added in one portion . after 1 hour of stirring at the same temperature , the mixture was gradually cooled to 20 ° c . in 2 hours and stirred at this temperature for 2 hours more . finally , the suspension was filtered under vacuum and the cake was washed twice with 100 ml of toluene . the product was used as a wet solid in the next step . ( hplc : 97 area %). 1 h nmr ( 400 mhz , dmso - d6 ): 12 . 38 ( 2h , s ); 8 . 39 ( 1h , d , j : 8 . 6 hz ); 8 . 02 - 7 . 11 ( 14h , m ); 4 . 90 ( oh , s ); 4 . 51 ( oh , s ); 3 . 99 ( 1h , t , j : 7 . 3 hz ); 3 . 34 ( 1h , d , j : 11 . 0 hz ); 3 . 27 ( 1h , d , j : 11 . 0 hz ); 3 . 06 ( 1h , td , j : 12 . 3 hz ; j : 4 . 9 hz ); 2 . 77 ( 2h , d , j : 15 . 4 hz ); 2 . 73 ( 1h , m ); 2 . 66 ( 2h , d , j : 15 . 4 hz ); 2 . 54 ( 1h , d , j : 12 . 7 hz ); 2 . 41 ( 1h , d , j : 12 . 7 hz ); 2 . 17 ( 2h , m ); 1 . 44 ( 6h , s ); 0 . 44 - 0 . 36 ( 2h , m ); 0 . 32 - 0 . 22 ( 2h , m ). ir ( kbr )= 3411 , 3052 , 2970 , 2922 , 2593 , 1727 , 1632 , 1599 , 1488 , 1437 , 1409 , 1376 , 1318 , 1223 , 1208 , 1153 , 1080 , 1026 , 961 , 927 , 861 , 840 , 760 , 729 , 694 , 598 , 471 cm − 1 . the wet solid obtained in example 15 was partitioned with 800 ml of toluene and 800 ml of an aqueous solution of nahco 3 5 %. the organic layer was separated , washed with 800 ml of water and concentrated to dryness by rotary evaporation under vacuum at 30 ° c . 29 . 7 g of a pale yellow solid were recovered . overall yield for the 2 steps : 39 % ( hplc : 96 area %). 5 ml of water were added to a 96 g of a toluene solution containing 10 g of ( r , e )-( 1 -(( 1 -( 3 -( 2 -( 7 - chloroquinolin - 2 - yl ) vinyl ) phenyl )- 3 -( 2 -( 2 - hydroxypropan - 2 - yl ) phenyl ) propylthio ) methyl ) cyclopropyl ) methyl methanesulfonate ; followed of 0 . 5 g of tetrabutylammonium hydrogen sulfate and 0 . 85 g of sodium cyanide . the mixture was stirred at 60 ° c . for 20 hours . then , it was cooled to room temperature and the organic layer was washed three times with 100 ml of water . finally , the outcome toluene solution was concentrated to dryness by rotary evaporation under vacuum at 30 ° c . 9 . 5 g were obtained . to a solution of 0 . 5 g ( 8 . 82 mmol ) of ( r , e )- 2 -( 1 -(( 1 -( 3 -( 2 -( 7 - chloroquinolin - 2 - yl ) vinyl ) phenyl )- 3 -( 2 -( 2 - hydroxypropan - 2 - yl ) phenyl ) propyl ) sulfanyl ) methyl ) cyclopropyl ) acetonitrile in 3 . 5 ml of toluene a solution of 8 . 82 mmol of the acid in acetonitrile or tetrahydrofurane was slowly added at room temperature . the solvent was distilled off and the theoretical amount of the salt was obtained as a yellow solid . the general example has been repeated using the corresponding acids indicated in the following examples : preparation of oxalate salt of the compound ( iii ) using oxalic acid . yield : 100 %; ir ( kbr ) ( cm − 1 ): 3420 , 2970 , 2925 , 1719 , 1626 , 1600 , 1486 , 1408 , 1205 , 1157 , 1 . 080 , 762 , 695 ; 1 h rmn ( 400 mhz , dmso - d6 ): 8 . 41 ( 1h , d , j : 8 . 7 hz ); 8 . 0 - 7 . 1 ( 14h , m ); 4 . 04 ( 1h , t , 7 . 3 hz ); 3 . 1 ( 1h , m ); 2 . 8 ( 1h , m ); 2 . 63 ( 2h , s ); 2 . 51 ( 2h , under semideuterated dmso ); 2 . 2 ( 2h , m ); 1 . 44 ( 3h , s ); 1 . 43 ( 3h , s ); 0 . 60 - 0 . 40 ( 4h , m ). preparation of malate salt of the compound ( iii ) using l -(−)- malic acid ; yield : 100 %; ir ( kbr ) ( cm − 1 ): 3436 , 2976 , 2930 , 1721 , 1628 , 1607 , 1498 , 1409 , 1161 , 1078 , 761 , 696 ; 1 h rmn ( 400 mhz , dmso - d6 ): 12 . 41 ( 1h , broad ); 8 . 40 ( 1h , d , j = 8 . 69 hz ); 8 . 0 - 7 . 1 ( 14h , m ); 4 . 91 ( 1h , s ); 4 . 26 ( 1h , dd , j 7 . 83 hz , j = 4 . 78 hz ); 4 . 04 ( 1h , t , 7 . 35 hz ); 3 . 11 - 3 . 01 ( 1h , m ); 2 . 80 - 2 . 70 ( 1h , m ); 2 . 61 ( 1h , dd , j = 15 . 66 hz , j = 4 . 80 hz ); 2 . 51 ( 2h , under semideuterated dmso ), 2 . 44 ( 1h , dd , j = 15 . 66 hz , j = 7 . 84 hz ); 2 . 26 - 2 . 10 ( 2h , m ); 1 . 44 ( 3h , s ); 1 . 43 ( 3h , s ); 0 . 60 - 0 . 40 ( 4h , m ). preparation of tartrate salt of the compound ( iii ) using l -(+)- tartaric acid ; yield : 100 %; ir ( kbr ) ( cm − 1 ): 3401 , 2970 , 2927 , 1726 , 1626 , 1605 , 1487 , 1408 , 1205 , 1130 , 1080 , 762 , 696 ; 1 h rmn ( 400 mhz , dmso - d6 ): 12 . 68 ( 1h , broad ); 8 . 41 ( 1h , d , j : 8 . 64 hz ); 8 . 04 - 7 . 04 ( 14h , m ); 4 . 91 ( 1h , s ); 4 . 31 ( 2h , s ); 4 . 04 ( 1h , t , j = 7 . 34 hz ); 3 . 12 - 3 . 00 ( 1h , m ); 2 . 81 - 2 . 70 ( 1h , m ); 2 . 64 ( 2h , s ); 2 . 51 ( 2h , under semideuterated dmso ); 2 . 26 - 2 . 07 ( 2h , m ); 1 . 44 ( 3h , s ); 1 . 43 ( 3h , s ); 0 . 60 - 0 . 40 ( 4h , m ). the following salts of the compound ( iii ) were also prepared using the process of the general example from the corresponding acids : maleate , fumarate , succinate , benzoate , 4 - hydroxymandelate , citrate and mandelate . to a solution of 3 . 14 g ( 5 . 53 mmol ) of ( r , e )- 2 -( 1 -(( 1 -( 3 -( 2 -( 7 - chloroquinolin - 2 - yl ) vinyl ) phenyl )- 3 -( 2 -( 2 - hydroxypropan - 2 - yl ) phenyl ) propyl ) sulfanyl ) methyl )- cyclopropyl ) acetonitrile in 21 . 5 ml of toluene a solution of 0 . 68 g ( 5 . 42 mmol ) of oxalic acid dihydrate in 10 ml acetonitrile was added at room temperature . the solution was concentrated under vacuum to half the initial volume and stirred at room temperature overnight . the outcome solid was filtered off and dried under vacuum . 2 . 71 g ( 71 % yield ) of a yellow solid were obtained . 1 h nmr ( 400 mhz , dmso - d6 ): 8 . 41 ( 1h , d , j : 8 . 7 hz ); 8 . 0 - 7 . 1 ( 14h , m ); 4 . 04 ( 1h , t , 7 . 3 hz ); 3 . 1 ( 1h , m ); 2 . 8 ( 1h , m ); 2 . 63 ( 2h , s ); 2 . 51 ( 2h , under semideuterated dmso ); 2 . 2 ( 2h , m ); 1 . 44 ( 3h , s ); 1 . 43 ( 3h , s ); 0 . 60 - 0 . 40 ( 4h , m ). ir ( kbr )= 3420 , 2970 , 2925 , 1719 , 1626 , 1600 , 1486 , 1408 , 1205 , 1157 , 1 . 080 , 762 , 695 cm − 1 . to a solution of 1 . 0 g ( 1 . 76 mmol ) of ( r , e )- 2 -( 1 -(( 1 -( 3 -( 2 -( 7 - chloroquinolin - 2 - yl ) vinyl ) phenyl )- 3 -( 2 -( 2 - hydroxypropan - 2 - yl ) phenyl ) propyl ) sulfanyl ) methyl )- cyclopropyl ) acetonitrile in 6 ml of toluene a solution of 0 . 303 g ( 1 . 73 mmol ) of benzensulfonic acid 90 % in 0 . 6 ml acetonitrile was added at room temperature . the solution was stirred at room temperature overnight . the outcome solid was filtered off and dried under vacuum . 0 . 96 g ( 75 % yield ) of a yellow solid were obtained . 1 h nmr ( 400 mhz , dmso - d6 ): 8 . 74 ( 1h , d , j : 8 . 7 hz ); 8 . 27 - 7 . 04 ( 19h , m ); 4 . 07 ( 1h , t , 7 . 3 hz ); 3 . 1 ( 1h , m ); 2 . 8 ( 1h , m ); 2 . 63 ( 2h , s ); 2 . 51 ( 2h , under semideuterated dmso ); 2 . 2 ( 2h , m ); 1 . 44 ( 3h , s ); 1 . 43 ( 3h , s ); 0 . 61 - 0 . 41 ( 4h , m ). ir ( kbr )= 3430 , 3050 , 2910 , 1625 , 1600 , 1480 , 1230 , 1150 , 1125 , 1020 , 990 , 690 , 610 cm − 1