Practical chemical and enzymatic technologies for (S)-1, 4-benzodioxan-2-carboxypiperizine intermediate in the synthesis of (S)-doxazosin mesylate

…, FX McConville, RF Rossi, DJ Olsson, DW Kessler…

Index: Fang; Grover, Paul; Han, Zhengxu; McConville, Fran X.; Rossi, Richard F.; Olsson, Damase J.; Kessler, Donald W.; Wald, Stephen A.; Senanayake, Chris H. Tetrahedron Asymmetry, 2001 , vol. 12, # 15 p. 2169 - 2174

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Citation Number: 26

Abstract

(S)-1, 4-Benzodioxan-2-carboxypiperazine (S)-2, the key chiral intermediate for the synthesis of (S)-doxazosin, was prepared utilizing two approaches:(i) enzymatic resolution of ethyl 1, 4-benzodioxan-2-carboxylate with an esterase (Serratia) followed by amide formation;(ii) direct resolution of 1, 4-benzodioxan-2-carboxypiperazine 2 with d-tartaric acid. An efficient process for the conversion of (S)-2 to (S)-doxazosin mesylate was developed ( ...