Method for synthesizing N-Boc-3-pyrrolidine formaldehyde

Abstract

The invention discloses a method for synthesizing N-Boc-3-pyrrolidine formaldehyde, which comprises the following steps of: (1) adding 1mol of glycine and 0.5 to 1.5mol of acrylonitrile into a methylbenzene solvent, refluxing the solution under the action of 1.5 to 2.5mol of paraformaldehyde, cooling and then performing suction filtering on the solution, concentrating the mother solution, distilling the mother solution under reduced pressure, and collecting the fraction of 102 to 105 degrees to obtain 3-cyanopyrrolidine; (2) adding 0.5mol of 3-cyanopyrrolidine obtained in the step (1) into dichloromethane, dripping 0.4 to 0.6mol of Boc acid anhydride into the solution at room temperature under the action of 0.5 to 0.75mol of triethylamine, performing room temperature reaction, washing the reaction solution by using hydrochloric acid solution, and separating, drying and concentrating the solution to obtain N-Boc-3-cyanopyrrolidine; and (3) dissolving 0.4mol of N-Boc-3-cyanopyrrolidine obtained in the step (2) into dichloromethane, cooling the solution, dripping 0.4 to 0.6mol of di-isobutyl aluminum hydride into the solution, dripping hydrochloric acid solution into the reaction solution after reaction to quench the reaction, separating the solution, concentrating the organic phase, distilling the concentrate under reduced pressure, and collecting the fraction of 110 to 114 degrees to obtain the N-Boc-3-pyrrolidine formaldehyde. The synthesizing method has a few steps, high yield and low cost, and is suitable for industrial large-scale production.

Description

technical field [0001] The invention relates to a method for synthesizing N-BOC-3-pyrrolidine formaldehyde, which belongs to the technical field of organic compound synthesis. Background technique [0002] N-BOC-3-pyrrolidine formaldehyde is an important synthetic raw material for many medicines, pesticides and auxiliary agents, such as channel receptor agonists, receptor modulators, etc., including the treatment of pain, central nervous system diseases, neuropathy, inflammation, etc. disease. In recent years, a series of new drugs containing N-BOC-3-pyrrolidine carboxaldehyde structure have been discovered, and the demand for this intermediate in the market is increasing day by day. [0003] Through our market survey, there is no company at home or abroad that has the ability to mass-produce this compound, and the existing production capacity is far from meeting the demand for this compound in the international market. [0004] Among the currently known synthetic methods ...

AI Technical Summary

Problems solved by technology

[0006] To sum up, the method in this patent requires benzylamine and chloromethyltrimethylsilane as raw materials to produce N-BOC-3-pyrrolidine formaldehyde through a seven-step reaction, and contains high-risk components such as catalytic hydrogenation. , Steps that require high equipment, many reaction steps, difficult to operate, high cost, difficult to use for scale-up production

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