Hydrogen Bromide → 2-Benzhydrylsulfanylacetic acid

Participants

Reaction Steps

Scheme 2 describes an industrial method for the preparation of Modafinil (II) wherein the all the reaction steps may be carried out in situ. In this scheme, the starting material is diphenylmethanol which is reacted with thiourea in the presence of HBr followed by basic hydrolysis and reaction with chloroacetic acid to form compound III. Hydrogen peroxide is then passed through the reaction mixture followed by acidification with hydrochloric acid to form (benzhydrylsulfinyl)acetic acid. The acid is reacted with dimethyl sulphate in presence of soda lye and sodium bicarbonate to obtain methyl(benzhydrylsulfinyl)acetate. After filtration methyl(benzhydrylsulfinyl)acetate is dissolved in methanol and ammonia is bubbled through the reaction mixture. After recrystallization and drying of the reaction mass Modafinil (II) is obtained with 41% total yield calculated from benzhydrol. The in-situ reaction scheme 2 is set out below.

Provenance & Evidence