Method ofr synthesizing S-(1)-2.2 dimethylcyclopropane formamide

Abstract

This invention relates to process for synthesizing S-(+)-2,2-dimethyl cyclopropane formyl amide, using penteneic acid as main raw material, after procedures of: esterification, cyclopropanization, hydrolyzation, acylation, salifying, partial crystallization and ammonolysis. advantages are: short reaction time, mild reaction condition, simple process, total yield is more than 15%, ee is larger than 95.6%.

Description

Technical field:

[0001] The invention relates to a method for synthesizing S-(+)-2,2-dimethylcyclopropanecarboxamide. Background technique:

[0002]

[0003] S-(+)-2,2-dimethylcyclopropanecarboxamide, whose molecular formula is shown in S-1, is a key intermediate for the synthesis of cilastatin (a kidney dehydrodipeptidase inhibitor), now Generally adopt the following two methods to make in the technology:

[0004] Graham et al. (J. Med Chem. 1987, 30, 1074) reported that 2,2-dimethyl-1,3-propanediol was used as a raw material and synthesized through six steps. This method not only has a long reaction time, but also involves the use of highly toxic potassium cyanide as a reactant and expensive quinine as a resolution reagent, so the danger to the human body or the environment is large and the cost is high.

[0005] S-1 is prepared by using the chiral raw material of S-(+)-2,2-dimethylcyclopropanecarboxylic acid with the molecular formula as S-2, through acid chloride an...

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