1251618-05-9Relevant articles and documents
Selective synthesis method of diltiazem chiral intermediate
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Paragraph 0018; 0031, (2016/10/10)
The invention provides a selective synthesis method of diltiazem chiral intermediate. The method is as below: using anisic aldehyde, chloroacetyl chloride and L-menthol as raw materials; first subjecting chloroacetyl chloride and L-menthol to an esterification reaction to obtain an intermediate 1; then subjecting the intermediate 1 with anisic aldehyde to a Darzens condensation reaction to produce diastereomer intermediates 2 and 3; refining to obtain an optically pure intermediate 3; reacting the intermediate 3 with o-aminothiophenol to obtain an intermediate 4; hydrolyzing the intermediate 4 to obtain an intermediate 5; and cyclizing the intermediate 5 to obtain a product. The invention has the advantages that the ester formed by chloroacetyl chloride and L-menthol is selective in the Darzens condensation reaction with anisic aldehyde to generate the more target product, and solubility difference between the target product and the isomer is used to directly obtain optically pure intermediate, without a complicated resolution process, and the yield is greatly improved. The method substantially increases the utilization rate of the main raw material anisic aldehyde and reduces cost.
