Preparation method of optically pure 3-amino-1-butanol

Abstract

The invention provides a method for preparing optically pure 3-amino-1-butanol. The method comprises the following steps: reacting benzamide and acetoacetate under the catalytic action of p-toluenesulfonic acid to generate 3-benzamido-2-crotonate; carrying out catalytic hydrogenation reaction by using a chiral rhodium-diphosphine ligand compound as an asymmetric hydrogenation catalyst to generate 3(R) / (S)-benzamidobutyrate at high selectivity; reducing ester carbonyl group with hydroborate to generate 3(R) / (S)-benzamido-1-butanol; and finally, carrying out hydrolysis and benzoyl removal with concentrated hydrochloric acid to obtain the optically pure 3(R) / (S)-amino-1-butanol. The method has the advantages of cheap and accessible raw materials, simple technical operation, no need of resolution, high yield, low cost, environment friendliness and high optical purity of the product, and is more suitable for industrial production.

Description

technical field [0001] The present invention relates to the preparation of chiral drugs. In particular, it relates to a preparation method of optically pure 3‐amino‐1‐butanol as a chiral drug intermediate. Background technique [0002] Optically active 3-amino-1-butanol is a key intermediate of many chiral drugs. Such as J.Org.Chem., 1977, 42:1650, it is reported that it is the key intermediate of the antineoplastic drug 4‐methyl cyclophosphamide; Teter.Lett., 1988, 29:231, it is reported that it can be derived into β‐ Lactam, so it is an important intermediate for the synthesis of penem antibiotics; Drugs.Of the Future 2012,37:697, it is reported that it is also the chirality of the anti-AIDS drug Dolutegravir (listed in the United States in 2013, trade name Tivicay) The key intermediate of the six-membered ring. [0003] The synthetic method of this compound mainly contains following several kinds: [0004] Tetrahedron Lett.1988,29(2), 231 reported the synthetic method...

AI Technical Summary

Problems solved by technology

It has two disadvantages: one is that chiral phenylethylamine is more expensive; the other is that solvent recrystallization is required to split a pair of epimers, and in order to achieve a product with optical purity that meets the requirements, repeated crystallization is required. times, leading to a decrease in yield

However, its shortcoming is that the yield of the first step condensation reaction and the last step carboxyl reduction reaction is low, and the yields of these two steps are only 55-61% and 47-54% respectively.

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