Synthesis of (S)-3-(N-Methylamino)-1-(2-thienyl) propan-1-ol: Revisiting Eli Lilly's Resolution-Racemization-Recycle Synthesis of duloxetine for its robust processes

…, M Ikunaka, T Inoue, J Matsumoto

Index: Fujima, Yoshito; Ikunaka, Masaya; Inoue, Toru; Matsumoto, Jun Organic Process Research and Development, 2006 , vol. 10, # 5 p. 905 - 913

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Citation Number: 44

Abstract

(±)-3-(N, N-Dimethylamino)-1-(2-thienyl) propan-1-ol (6), prepared from 2-acetylthiophene (4) in a two-step overall yield of 79%, is resolved into (S)-6 of 93% ee as its diastereomeric salt (8) with (S)-mandelic acid (7) according to Eli Lilly's procedures developed for the resolution-racemization-recycle (RRR) synthesis of duloxetine (2) with some modifications in terms of practicality. On its liberation from 8,(S)-6 undergoes N-demethylative ethyl ...