Method for synthesizing 3-aza-bicyclo[4.1.0]heptane-6-formic acid with protective group

A synthetic method and a technology of protecting groups, which are applied in the field of synthesis of 3-aza-bicyclo[4.1.0]heptane-6-carboxylic acid, can solve the problems of short synthetic route and overall yield, and achieve short reaction time and high yield. High efficiency and mild reaction conditions
CN102070526BActive Publication Date: 2013-12-25上海药明康德新药开发有限公司 +2
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
上海药明康德新药开发有限公司
Publication Date
2013-12-25

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Abstract

The invention relates to a method for preparing 3-aza-bicyclo[4.1.0]heptane-6-formic acid with a protective group, and mainly solves the technical problem that multi-step chromatographic purification is needed in the conventional process for preparing the 3-aza-bicyclo[4.1.0]heptane-6-formic acid. The method comprises the following steps of: performing reflux alkylation reaction on conventional and readily available ethyl isonicotinate serving as a raw material and halohydrocarbon in alcohol solution to obtain quaternary ammonium; performing cyanoborohydride reaction to obtain amino-protected 1,2,3,6-tetrahydropyridine-4-ethyl formate; not performing purification, and directly performing ring-closing reaction to obtain a three-membered ring; and performing alkaline hydrolysis reaction to obtain amino-protected 3-aza-bicyclo[4.1.0]heptane-6-formic acid. The 3-aza-bicyclo[4.1.0]heptane-6-formic acid with the protective group is an important medicinal intermediate.
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Description

Technical field:

[0001] The invention relates to a method for synthesizing protected 3-aza-bicyclo[4.1.0]heptane-6-carboxylic acid. Background technique:

[0002] 3-Aza-bicyclo[4.1.0]heptane-6-carboxylic acid is a useful drug intermediate, and the synthetic method reported in the literature is obtained through multi-step reactions with 4-aminopropionic acid: first esterification, enzymatic Alkylation of the propyl group followed by protection of the amino group gave compound 4, the α-halogenated compound 4, followed by catalyst Pd(PPh 3 ) 4 In the presence of 1,8-bisdimethylaminonaphthalene (proton sponge) reagent treatment to obtain the six-membered ring compound 6; finally the alkali action to close the three-membered ring, hydrolysis to obtain the desired 3-aza-bicyclic ring with a protective group [4.1.0] Heptane-6-carboxylic acid.

[0003] Literature synthesis route:

[0004]

[0005] The synthetic route provided in the literature has long steps, low overall yiel...

Claims

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