the reaction mixture was stirred at u2212 65 to u2212 75 u00b0 c for one hour the reaction mixture was then warmed to 40 u00b0 c and stirred at this temperature for three hours solvent was removed under vacuum and the reaction mixture was diluted with water 700 ml and methanol 300 ml activated charcoal 4 g was then added and the mixture was refluxed for 30 minutes the heterogeneous mixture was filtered through hyflo and the hyflo bed was washed with methanol 300 ml and water 150 ml the aqueous methanolic layer was then extracted with hexanes 2 u00d7 500 ml and acidified with 10 sulfuric acid to ph 2 8 u00b1 0 5 the desired product was then extracted with dichloromethane 2 u00d7 500 ml the combined dichloromethane layer was washed with water 2 u00d7 300 ml and concentrated in vacuo to afford the desired isotretinoin crystallization from methanol 200 ml afforded isotretinoin 44 g in greater than 99 hplc purity the tretinoin content was less than 0 1 by hplc under an atmosphere of nitrogen a solution of n butyl lithium in hexane 20 ml 15 was added to a solution of diisopropylamine 2 7 g 0 027 mole in diisopropyl ether 10 ml at u2212 74 u00b0 c and the reaction mixture stirred for 0 5 hour to this methyl 3 3 dimethyl acrylate 2 51 g 0 022 mole was added at u2212 74 u00b0 c.