Preparing 6,6-dimethyl-azabicyclo-methyl carboxylate, comprises e.g. substituting hydroxy-dimethyl-hexane-dimethyl-propyl ester by hydroxyl compound and cyaniding obtained pyrrolidine compound to give dimethylpropyl-azabicyclo-carboxylate

摘要

Preparing (1R,2S,5S)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-methyl carboxylate (A), comprises (a) substituting (1R,5S)-2-hydroxy-6,6-dimethyl-bicyclo[3.1.0]hexane-3-carboxylic acid 1,1-dimethyl-propyl ester by hydroxyl compound to give pyrrolidine compound (I), (b) cyaniding (I) to give 1,1-dimethylpropyl (1R,2S,5S)-2-cyano-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carboxylate, and (c) deprotecting the 1,1-dimethylpropyl (1R,2S,5S)-2-cyano-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carboxylate to give (A). Preparing (1R,2S,5S)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-methyl carboxylate (A), comprises (a) substituting (1R,5S)-2-hydroxy-6,6-dimethyl-bicyclo[3.1.0]hexane-3-carboxylic acid 1,1-dimethyl-propyl ester by hydroxyl compound of formula (Alk-OH) to give pyrrolidine compound of formula (I), (b) cyaniding (I) to give 1,1-dimethylpropyl (1R,2S,5S)-2-cyano-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carboxylate, and (c) alcoholysis and deprotecting the 1,1-dimethylpropyl (1R,2S,5S)-2-cyano-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carboxylate to give (A).Alk = 1-6C alkyl. Independent claims are included for: (1) (1R,5S)-6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester compound of formula (II); and (2) the preparation of boceprevir, comprising (A). Either R1, R2 : H; and R2 : -OH, O-Alk or -CN; or R1R2 : (C=O). [Image] [Image] ACTIVITY : Antiinflammatory; Hepatotropic; Virucide. MECHANISM OF ACTION : None given.