Sduty On The Synthesis Of(S)-2,2-diphenyl-2-(Pyrrolidin-3-yl)Acetamide

Darifenacin is a good medicine for curing overactive bladder.(S)-2,2-diphenyl-2-(pyrrolidin-3-yl) acetamide is an important intermediate for syn-thesizing Darifenacin.We design a new synthesis route for (S)-2,2-diphenyl-2-(pyrrolidin-3-yl) acetamide from L-malic acid and benzylamine. The synthesis process is optimized by investigating experimental conditions of every step reaction. We synthesize successfully six compounds including target molecule and its intermediates, and confirm their structure by IR and1H NMR.Our synthesis route includes six steps. The fist step concerns cyclization reaction of L-malic acid and benzylamine, and the yield is71%; the second step concerns reduction reaction from diimide to amine, and the yield is81%; the third step concerns sulfonlytion, and the yield is59%; the fourth step concerns SN2reaction of sulfonic esters and diphenylacetonitrile, and the yield is70%; the fifth step concerns deprotection of amido, and the yield is82%; the sixth step concerns hydrolysis reaction from nitrile to amide, and the yield is57%. The total yield of (S)-2,2-diphenyl-2-(pyrrolidin-3-yl) acetamide is 11%.