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

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• 作者：Zhengxu Han ; Stefan G. Koenig ; Hang Zhao ; Xiping Su ; Surendra P. Singh ; Roger P. Bakale
• 刊名：Organic Process Research & Development
• 出版年：2007
• 出版时间：July 2007
• 年：2007
• 卷：11
• 期：4
• 页码：726 - 730
• 全文大小：80K
• 年卷期：v.11,no.4(July 2007)
• ISSN：1520-586X

文摘

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