Method for the preparation of (3S, 3S′) 4,4′-disulfanediylbis (3-aminobutane 1-sulfonic acid)

摘要

The present invention relates to a new method for the preparation of (3S,3S′) 4,4′-disulfanediylbis(3-aminobutane 1-sulfonic acid) in five steps from (S)-ethyl 2-(benzyloxycarbonylamino)-4-(neopentyloxysulfonyl)butanoate A.

主权项

1. A process for preparing (3S,3S′) 4,4′-disulfanediylbis(3-aminobutane 1-sulfonic acid) from (S) ethyl 2-(benzyloxycarbonylamino) 4-(neopentyloxysulfonyl)butanoate A comprising the steps of:
(a) reducing the ethyl ester of A to give (S) neopentyl 3-(benzyloxycarbonylamino) 4-hydroxybutane 1-sulfonate B; (b) reacting the alcohol B with methanesulfonic anhydride or methanesulfonyl chloride in presence of a base to give (S) neopentyl 3-(benzyloxycarbonylamino) 4-(methylsulfonyloxy)butane 1-sulfonate C; (c) reacting the mesylated alcohol C with potassium thioacetate to give (S) 2-(benzyloxycarbonylamino) 4-(neopentyloxysulfonyl)butyl thioacetate D; (d) dimerizing D to give (3S,3S′) neopentyl 4,4′-disulfanediylbis(3-(benzyloxycarbonylamino)butane 1-sulfonate) E; and (e) deprotecting sulfonic ester and amine groups of E to give (3S,3S′) 4,4′-disulfanediylbis(3-aminobutane 1-sulfonic acid).