Preparation method of O-tert-butyl-L-serine methyl ester and O-tert-butyl-L-serine aqueous solution

Abstract

The invention relates to the technical field of medical chemistry, in particular to a preparation method of O-tert-butyl-L-serine methyl ester and an O-tert-butyl-L-serine aqueous solution, which comprises the following steps: (a) adding L-serine and a methanol solution into a reaction container, dropwise adding SOCl2 into the reaction container while stirring, and carrying out reflux reaction, concentration, crystallization and drying to obtain L-serine methyl ester hydrochloride; and (b) adding the L-serine methyl ester hydrochloride prepared in the step (a) into tert-butyl acetate, then adding a catalyst, and conducting reacting at room temperature while stirring to obtain the O-tert-butyl-L-serine methyl ester. In the preparation method provided by the invention, the reaction is carried out in a liquid phase, so that the method is safe and pollution-free. O-tert-butyl-L-serine methyl ester is prepared by reacting L-serine methyl ester hydrochloride with butyl acetate at room temperature, isobutene does not need to be added as a raw material, the safety is high, the total yield of the product is 72% or above, and the yield is high.

Description

[0001] This application is a branch of the application date of September 25, 2018, the application number of 201811116476.6, and the title of the invention "A Preparation Method for N-(9-fluorenylmethoxycarbonyl)-O-tert-butyl-L-serine". case application. technical field [0002] The invention relates to the technical field of medicinal chemistry, in particular to a preparation method of O-tert-butyl-L-serine methyl ester and O-tert-butyl-L-serine aqueous solution. Background technique [0003] The current preparation method of N-(9-fluorenylmethoxycarbonyl)-O-tert-butyl-L-serine has many steps in the preparation process, which will lead to N-(9-fluorenylmethoxycarbonyl)-O- The preparation cost of tert-butyl-L-serine is relatively high, and the preparation time is also long at the same time. The traditional synthesis preparation route will lead to very easy racemization in the original synthesis process, the optical purity is not high, and the process parameters are not easy ...

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Problems solved by technology

[0003] The current preparation method of N-(9-fluorenylmethoxycarbonyl)-O-tert-butyl-L-serine has many steps in the preparation process, which will lead to N-(9-fluorenylmethoxycarbonyl)-O- The preparation cost of tert-butyl-L-serine is relatively high, and the preparation time is also long at the same time. The traditional synthesis preparation route will lead to very easy racemization in the original synthesis process, the optical purity is not high, and the process parameters are not easy to control; Due to the presence of multiple steps in the preparation process, it is easy to cause more impurities in the preparation process, which increases the burden on the subsequent purification and impurity removal work, resulting in increased preparation costs; the traditional preparation of N-(9-fluorenylmethoxycarbonyl )-O-tert-butyl-L-serine The final product generated by the method still has the problem of low purity, the single impurity is about 0.3%, the product is difficult to dry, and the moisture content is difficult to dry to below 1%.

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