Development of a Large-Scale Stereoselective Process for (1R,4S)-4-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine Hydrochloride

A convenient, multikilogram-scale, stereoselective process for the synthesis of (1 R,4 S )-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, 4 S )-5 from ( S )-tetralone (4 S )-3 and ( R )- tert -butylsulfinamide ( R s )-4, and its stereoselective reduction with 9-BBN to produce the (1 R )-amine center of 1 . The process has been scaled up to multikilogram scale and gives 1 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.