3-(S)-(1-氨甲酰基-1,1-二苯甲基)吡咯烷的合成

Synthesis of 3-(S)-(1-Carbamoyl-1,1-diphenylmethyl) pyrrolidine

反式-4-羟基-L-脯氨酸经脱羧、N-Boc保护和氯代反应制得N-Boc-3-(S)-氯吡咯烷,在叔丁醇钾作用下与二苯乙腈缩合得N-Boc-3-(S)-(1-氰基-1,1-二苯甲基)吡咯烷,再经水解、脱保护、经L-(+)-酒石酸处理后碱化制得氢溴酸达非那新中间体3-(S)-(1-氨甲酰基-1,1-二苯基甲基)吡咯烷,总收率约14%。

3-（S）-（1-Carbamoyl-1,1-diphenylmethyl）pyrrolidine,an intermediate of derifenacin hydrobromide,was synthesized from trans-4-hydroxy-L-proline by decarboxylation,N-Boc protection and chlorination to give N-Boc-3-（S）-chloropyrrolidine,which was subjected to condensation with diphenylacetonitrile in presence of potassium t-butoxide,hydrolysis,deprotection,treatment with L-（＋）-tartaric acid and then alkalization.The overall yield was about 14%.