Preparation method of (S)-N-Boc-3-hydroxypiperidine

Abstract

The invention discloses a preparation method of (S)-N-Boc-3-hydroxypiperidine, wherein the preparation method includes the following steps: adding N-Boc-3-piperidone and water into a reaction kettle,adding a sodium phosphate buffer solution, mixing and stirring evenly, adding glucose, then adjusting the pH to 7 with phosphoric acid, controlling the temperature to 25-35 DEG C, then adding immobilized mixed enzyme particles prepared in the step (2), stirring, carrying out a reaction for 24 h, followed by, filtering, recycling the immobilized mixed enzyme particles, extracting the filtrate withethyl acetate, carrying out reduced pressure distillation, and recrystallizing with petroleum ether to obtain (S)-N-Boc-3-hydroxypiperidine. The preparation method has the advantages of simple operation, mild conditions, fewer by-products, high product purity and relatively high product yield.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a preparation method of (S)-N-Boc-3-hydroxypiperidine. Background technique [0002] Chirality is a basic attribute in nature, and many basic structural units in organisms have chirality. Chiral drugs refer to drugs containing chiral centers in their molecular structures, including single stereoisomers, unequal mixtures of two or more stereoisomers, and racemates. Piperidine is an important class of pharmaceutical intermediates and chemical intermediates. It plays an important role in the synthesis of chiral drugs. A variety of high value-added pharmaceutical intermediates. Among them, 3-hydroxypiperidine, which has a chiral structure, plays an important role in lowering blood pressure, anti-tumor, and anti-coccidiosis. [0003] N-Boc-3-hydroxypiperidine is an important derivative of 3-hydroxypiperidine, and it is also an important pharmaceutical intermediate. This compound ca...

AI Technical Summary

Problems solved by technology

The biocatalytic method mainly has the following approaches: (1) take N-Boc-3-piperidone as raw material, reduce and introduce chiral center by ketoreductase, although this method can utilize the substrate to the greatest extent, the ketone used Reductase, coenzyme and lactate dehydrogenase for regeneration are expensive and easily inactivated; (2) Selective resolution with lipase can distribute and obtain (S) and (R) type 3-hydroxypiperidine , but the resolution yield of lipase is still low, and the separation of products is more complicated, and it is difficult for industrial production

The chemical synthesis method mainly contains the following methods: (1) using L-malic acid, L-Glu or L-Asp, etc. as raw materials, through multi-step reactions such as condensation and reduction, to obtain the target product, the process is complicated, and the raw materials are relatively Expensive; (2) use 3-hydroxypiperidine as raw material, after chemical resolution, prepare chiral alcohol by recrystallization, this method is easy to operate, but the yield is low