(r)-Asymmetric preparation method of albuterol hydrochloride

Abstract

The invention relates to a novel method for asymmetric syntheses of (R)-salbutamol hydrochloride by using a high-efficiency chiral catalyst. The method comprises the following steps: 1) subjecting salicylaldehyde and halogenoacetyl halide to Friedel-Crafts acylation so as to obtain halogenated ketone; 2) subjecting the obtained halogenated ketone to aminolysis with tert-butylamine and then carrying out hydrolysis and deprotection so as to obtain salicylaldamino ketone; and 3) reducing the salicylaldamino ketone into a crude product of (R)-salbutamol in the presence of a chiral borane catalyst derived from chiral aminoalcohol and carrying out purification and salt formation of hydrochloric acid so as to obtain the high purity (R)-salbutamol hydrochloride.

Description

technical field

[0001] The invention relates to a novel asymmetric synthesis method for synthesizing (R)-salbutamol and its hydrochloride with the participation of a high-efficiency chiral borane catalyst. Background technique

[0002] (R)-Salbutamol ((R)-Salbutamol), chemical name (R)-α-[[(1,1-Dimethylethyl)-amino]methyl-4-hydroxy-1,3-benzene Dimethanol, a β-2-antagonist used as a bronchodilator, has a good market prospect. Its structural formula is as follows:

[0003]

[0004] There are many example reports about the chemical methods and physical methods for the preparation of levosalbutamol at present. These methods can be divided into two categories: 1) Synthesize the racemate of albuterol first, and then obtain chiral products by chromatographic separation or chemical resolution, such as patents CN1382685A, CN1927813A, CN1934067A, CN102260179A and literature Chinese Journal of Pharmaceutical Industry, 2006 , 37(6), 376, etc.; 2) Levosalbutamol was directly synthe...

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