An improved method for preparing 5R-benzyloxyaminopiperidine-2S-formate oxalate

摘要

The present invention relates to an improved process for the preparation of 5R-benzyloxyaminopiperidine-2S-formate oxalate. The present invention relates to a process for preparing a compound III by a substitution reaction of L-glutamic acid or L-glutamic acid sodium salt with chloracetic acid under an alkaline condition as a starting material, esterifying the compound III with an alcohol in the presence of an acidic reagent, , Compound IV is subjected to an intramolecular condensation ring forming reaction, a hydrolytic decarboxylation reaction, an esterification reaction under the action of a strong base to obtain Compound V, and Compound V is condensed with benzyloxy ammonia hydrochloride in the presence of a base Compound VI is obtained, compound VI is reduced, chiral separation is performed to obtain 5R-benzyloxyaminopiperidine-2S-formate oxalate (IIb), and the compound (IIb) is neutralized to give 5R-benzyloxyaminopiperidine -2S-formate (IIa). The obtained 5R-benzyloxyaminopiperidine-2S-formate (IIa) and 5R-benzyloxyaminopiperidine-2S-formate oxalate (IIb) are used in the preparation of Avibactam. In the present invention, raw materials are cheap, easy to obtain, have high reaction selectivity, and are eco-friendly in the production process.