3 od u03b4 7 58 m 2h 7 03 m 4h 4 27 m 2h 4 07 m 3h 3 75 m 2h 3 30 m 1h 3 06 m 1h 1 22 m 3h step 1 u2014 formation of 1 4 4 cyanophenoxy 3 fluorophenyl sulfonyl 4 boc piperazine 2 r carboxylic acid piperazine 2 r carboxylic acid dihydrochloride 1 25 g 6 1 mmol dioxane 15 mls and water 6 0 mls were combined and cooled in an icebath 9n naoh 2 0 mls 18 mmol was added slowly with stirring followed by boc 2 o 1 35 g 6 2 mmol the reaction mixture was allowed to warm to room temperature and stirred for an additional 3 4 hrs et 3 n 1 8 mls 13 mmol was added followed by 4 cyanophenoxy 3 fluorophenylsulfonyl chloride 2 00 g 6 4 mmol the reaction mixture is stirred at room temperature for 1 2 hrs then concentrated in vacuo the resulting residue was partitioned between 1 0n hcl and etoac phases were separated and the aqueous phase was further extracted with etoac 2 u00d7 combined etoac extractions were washed with 1 0n hcl 1 u00d7 saturated nacl 1 u00d7 dried mgso 4 and concentrated in vacuo the resulting residue is purified by flash chromatography 7 3 hexanes etoac 1 acoh to give the desired product 1 1 g 35 lc ms calcd for m u2212 h u2212 504 1 found 504 3 step 2 methyl 1 4 4 cyanophenoxy 3 fluorophenyl sulfonyl 4 boc piperazine 2 r carboxylate was made in the same manner as example.