Synthesis of (1R)‐1‐(4‐Bromophenyl)‐2,2,2‐trifluoroethan‐1‐amine Hydrochloride through Diastereoselective Trifluoromethylation of a Chiral Sulfinimine

Abstract

AbstractAn efficient three‐step synthesis of (1R)‐1‐(4‐bromophenyl)‐2,2,2‐trifluoroethan‐1‐amine hydrochloride (1) starting from inexpensive and readily available starting materials was developed. The sequence features a highly diastereoselective trifluoromethylation of a chiral sulfinimine using the Rupert–Prakash reagent TMSCF3 in combination with K3PO4 as an initiator. The diastereomeric purity of the resulting sulfinamide was further improved by direct precipitation of the desired diastereomer from the reaction mixture upon addition of water. The chiral auxiliary was then removed under acidic conditions, resulting in the isolation of chiral benzylamine 1 as its hydrochloride salt in 71 % overall yield and excellent purity (LC/MS: >99 % a/a; e.r.=99 : 1).