op7000589_si_002.pdf (289.07 kB)
Development of a Large-Scale Stereoselective Process for (1R,4S)-4-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine Hydrochloride
journal contribution
posted on 2007-07-20, 00:00 authored by Zhengxu Han, Stefan G. Koenig, Hang Zhao, Xiping Su, Surendra P. Singh, Roger P. BakaleA 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 (Rs,4S)-5 from (S)-tetralone (4S)-3 and (R)-tert-butylsulfinamide (Rs)-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 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.