Process for the production of tertiary alcohols

Abstract

Tertiary alcohols are prepared by reacting carboxylic esters with Grignard reagents in ethereal solvents in the presence of lanthanum trichloride and lithium chloride. The method is particularly suitable for the production of (aS)-a-[3-[(1E)-2-(7-chloro-2-quino- linyl)ethenyl]phenyl]-2-(1-hydroxy-1-methylethyl)benzenepropanol of formula (A) which is an intermediate in the production of montelukast.

Description

technical field The present invention relates to the production method of the tertiary alcohol of formula (I) where R 1 for C 1-4 Alkyl, Q is C 1-10 Alkyl, C 2-10 Alkenyl, C 3-8 Cycloalkyl, aryl or heteroaryl or an organic moiety consisting of any two or more of the foregoing, C 1-10 Alkyl, C 2-10 Alkenyl, C 3-8 Each of cycloalkyl, aryl and heteroaryl is optionally replaced by one or more selected from hydroxyl, fluorine, chlorine, amino, C 1-4 Alkylamino and di(C 1-4 Alkyl) amino substituents are substituted. Background technique Tertiary alcohols with two lower alkyl groups on the methanolic carbon are valuable intermediates in the synthesis of a variety of pharmaceutically active compounds. For example, (αS)-α-[3-[(1E)-2-(7-chloro-2-quinolyl)vinyl]phenyl]-2-(1-hydroxyl-1-methyl Ethyl)-phenylpropanol is known as montelukast (1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)vinyl]phenyl]-3- [2-(1-Hydroxy-1-methylethyl)phenyl]propyl]sulfur]methyl]cyclopropaneacet...

AI Technical Summary

Problems solved by technology

In addition, the activation of cerium trichloride is lengthy and the activated cerium trichloride is not soluble in ethereal solvents such as tetrahydrofuran, which leads to heterogeneous reaction mixtures

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