Synthesis and preparation process of lamivudine intermediate HDMS

Abstract

The invention discloses a synthesis and preparation process of a lamivudine intermediate HDMS, which belongs to the field of organic synthetic medicaments. The synthesis and preparation process is characterized in that a preparation method of glyoxylic acid menthol ester comprises the following steps of: under the catalysis of concentrated sulfuric acid, performing a reflux reaction on L-menthol and glyoxylic acid, wherein a reactive solvent is cyclohexane; judging the reaction end point through a gas phase chromatography, and then cooling and washing the mixture; reacting an organic layer with solution of sodium bisulfite at the temperature of between 20 and 30 DEG C; judging the reaction end point through the gas phase chromatography, and then washing the mixture by using the cyclohexane; reacting an aqueous layer with methanol at the temperature of between 20 and 30 DEG C; and washing the mixture after filtering and drying the mixture to obtain the glyoxylic acid menthol ester. By using the synthesis and preparation process, the condition is milder, the operation is simpler and more convenient and the reaction processes are easier to control, so the product production yield and the quality stability are improved, and the cost of the lamivudine intermediate HDMS is greatly reduced.

Description

Technical field: [0001] The invention belongs to the field of organic synthetic medicines, in particular to a synthesis and preparation process of a lamivudine intermediate HDMS. Background technique: [0002] Lamivudine is a drug raw material with good antiviral activity. It is mainly used for anti-hepatitis B and anti-AIDS virus. It is the main active ingredient in the current treatment of hepatitis B and AIDS cocktail therapy. Its synthesis requires the excessive synthesis of intermediates. . [0003] Molecular formula of lamivudine intermediate HDMS: C 15 h 17 o 6 N 3 S.H 2 O, its chemical name: (2R-cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-1H-pyrimidin-2-one salicyl salt. [0004] English name: 2(R)-(HYDROXY METHYL)-5(S)CYTOSIN-1’-YL-1, 3-OXATHIOLANE SALICYLICACIDSALT. [0005] The structural formula is: [0006] [0007] In the synthesis process of lamivudine intermediate, domestic and foreign public reports, such as US5047407, Xu Fengjie, Yang Y...

AI Technical Summary

Problems solved by technology

[0013] The present invention discloses a production process in order to overcome various technical problems such as insufficient mild process conditions, insufficient operation and low yield in the existing HDMS synthesis process in the production process of menthyl glyoxylate CME-I Simple, easy to operate, mild reaction conditions, and a synthetic preparation process with increased yield and greatly reduced cost

Images