Development of a large-scale stereoselective process for (1R,4S)-4-(3,4-dichlorophenyl)-1 2,3,4-tetrahydronaphthalen-1-amine hydrochloride

作者：Han Zhengxu; Koenig Stefan G; Zhao Hang; Su Xiping; Singh Surendra P^*; Bakale Roger P

来源：Organic Process Research & Development, 2007, 11(4): 726-730.

DOI：10.1021/op7000589

A convenient, multikilogram-scale, stereoselective process for the synthesis of (1R,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine hydrochloride 1 is described. The key steps involve synthesis of sulfinyl imine (R-s,4S)-5 from (S)tetralone (4S)-3 and (R)-tert-butylsulfinamide (R-s)-4, and its stereoselective reduction with 9-BBN to produce the (1R)-amine center of 1. The process has been scaled up to multikilogram scale and gives I in an overall yield of > 50% with a chemical purity of 99.7 A% by HPLC and stereochemical purity of > 99.9% by chiral HPLC.

• 出版日期2007-8