Method for enzymatic synthesis of mono-4-nitrobenzyl malonate

Abstract

The invention relates to a method for synthesizing mono-4-nitrobenzyl malonate. The method comprises the steps of adding para-nitrobenzyl alcohol, malonic acid or malonate and a reaction solvent to a reaction flask at a mol ratio of 1: (1-10): (10-50); heating in a water bath until being balanced; adding lipase and a water absorbent to the reaction flask at a mol ratio of (0.1-1): (0-100) with the para-nitrobenzyl alcohol; controlling temperature at 30-50 DEG C, reacting for 10-48 hours, filtering to remove the lipase to obtain a reaction solution, and carrying out reduced pressure distilling on the reaction solution to remove the solvent, to obtain reaction residue; adding a mixing solution of an organic solvent and a salt solution to the reaction residue, stirring and layering, acidifying an obtained water phase, carrying out suction filtering and drying to obtain the mono-4-nitrobenzyl malonate. The method is easily available in raw materials, few in reaction step, moderate in reaction condition, few in side product, and simple and convenient to operate; the method, because the adopted organic solvent can be recycled, is low in environmental impact, simple in post-treatment, relatively high in production purity and yield, and suitable for industrial production.

Description

Technical field: [0001] The invention relates to a method for preparing a p-nitrobenzyl alcohol malonate pharmaceutical intermediate, in particular to a method for enzymatically synthesizing p-nitrobenzyl malonate. Background technique: [0002] p-Nitrobenzyl alcohol malonate is a class of important biomedical intermediates and an important industrial raw material for the preparation of antibiotic drugs. [0003] The chemical name of p-nitrobenzyl malonate is: Mono-4-nitrobenzyl Malonate, the CAS number is: 77359-11-6, and the chemical structure is: [0004] [0005] p-nitrobenzyl alcohol malonate can be prepared from malonic acid and p-nitrobenzyl alcohol through esterification, alkali-acid adjustment and refining (see US5087734); it can also be prepared from malonate bis(4-nitrobenzyl alcohol phenylmethyl) esters and malonic acid are prepared by reacting in the presence of a catalyst (referring to US5516934); however, the methods disclosed in these documents have high ...

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Problems solved by technology

[0005] p-nitrobenzyl alcohol malonate can be prepared from malonic acid and p-nitrobenzyl alcohol through esterification, alkali-acid adjustment and refining (see US5087734); it can also be prepared from malonate bis(4-nitrobenzyl alcohol phenylmethyl) esters and malonic acid are prepared by reacting in the presence of a catalyst (referring to US5516934); however, the methods disclosed in these documents have high raw material costs, large reaction energy consumption, and low yields (prone to generate by-product propane Dibenzyl diacid), and product purity and post-processing methods still need to be improved

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