Preparation method of 4-AA key intermediate epoxy butylamide

Abstract

The invention relates to a preparation method of 4-AA key intermediate epoxy butylamide. The preparation method comprises the steps that (1) synthesis of epoxy butyric acid is conducted: a starting material L-threonine is cyclized under diazotization and strong alkaline conditions to obtain the epoxy butyric acid; (2) synthesis of amino compounds is conducted: aminoanisole and chloroacetyl compounds (including ketone and esters) under the action of organic base are refluxed and react to obtain the amino compounds; and (3) synthesis of the epoxy butylamide is conducted: under the catalytic activation of acyl chloride, an amidation of the epoxy butylamide and the amino compounds is conducted to obtain the target product epoxy butylamide. The preparation method has the technical advantages that dosage of alkali and water is greatly reduced, dosage of organic extractants is correspondingly reduced, and at the same time, use of a phase transfer catalyst is avoided; the cost of raw materialsis lowered, and reaction time is shortened.

Description

technical field

[0001] The invention relates to a method for synthesizing a pharmaceutical intermediate, in particular to a method for preparing a key intermediate of 4-AA, epoxybutyramide. Background technique

[0002] 4-AA, whose chemical name is (3R,4R)-3-[(1R)-tert-butyldimethylsilyloxyethyl]-4-acetoxy-2-azetidinone, is a synthetic carbon An important intermediate of pendene antibiotics, high-efficiency antibacterial drugs carbapenem antibiotics play an important role in clinical anti-infection treatment, especially in the treatment of infections caused by drug-resistant bacteria, due to their strong antibacterial effect and small side effects. status. The chemical structural formula of 4-AA is as follows:

[0003] The molecular skeleton of 4-AA is characterized by a four-membered lactam ring, a silane-protected α-hydroxyethyl group on the 3rd carbon, three chiral centers, and an acetoxy group on the 4th carbon. The establishment of quaternary lactam ring and three ch...