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

(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 est erase (Serratia) followed by an-de formation; (ii) direct resolution of 1,4 -benzodioxan-2-carboxypiperazine 2 with D-tartaric acid. An efficient proce ss for the conversion of (S)-2 to (S)-doxazosin mesylate was developed (80% yield, 99.9% e.e.). (C) 2001 Elsevier Science Ltd. All rights reserved.