Simple synthesis process of anxiolytic drug lorazepam intermediate

Abstract

The invention discloses a simple synthesis process of an anxiolytic drug lorazepam intermediate. The simple synthesis process comprises the steps of putting N-(2-chloroethyl)acetamide, triethylamine and dichloromethane into a reaction bottle; stirring the mixture in an ice water bath; dropwise adding an o-nitrobenzyl chloride DCM (Dichloromethane) solution to the ice water bath; removing the ice water bath; separating the liquid; extracting the liquid with dichloromethane, and combining organic phases; drying the combined organic phase; concentrating the organic phase to dryness under reducedpressure to obtain a compound (1); putting the compound (1), acetic acid and ethanol into the reaction bottle for stirring; adding iron powder to the mixture to perform a temperature rise reaction; extracting the mixture twice with toluene, and combining the organic phases; drying the combined organic phase; filtering the organic phase; and collecting a filtrate to obtain a toluene solution of a compound (2); stirring the toluene solution of the compound (2) and potassium iodide, preserving heat until the raw materials are completely reacted; extracting an aqueous phase once with toluene, andcombining the organic phases; drying the combined organic phase; filtering the organic phase; collecting a filtrate; concentrating the filtrate to dryness under reduced pressure; adding methyl tert-butyl ether, refluxing and pulping, cooling and separating the material; and filtering the material to obtain a final product. The yield of the two steps is 84.2% and the purity is 99%. According to thesimple synthesis process of the anxiolytic drug lorazepam intermediate disclosed by the invention, the raw materials are simple and easy to obtain, the operation is simple and convenient, the yield is high, the three wastes are less, and the synthesis process is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a simple and convenient synthesis process of an anti-anxiety drug lorazepam intermediate. Background technique [0002] Anxiety disorder, also known as anxiety neurosis, is the most common type of neurosis. The main feature is the experience of anxiety, which can be divided into two forms: generalized anxiety and panic attacks. The main manifestations are: nervousness and worry without a clear objective object, restlessness, palpitations, hand tremors, sweating, frequent urination, and restlessness in movement, etc., which seriously affect the physical and mental health of patients. Among the anti-anxiety drugs, Lorazepam (Lorazepam), as a drug with better efficacy, is deeply trusted by the majority of patients. Lorazepam is a benzodiazepine anxiolytic, its full name is 7-chloro-5-(2-chlorobenzene)-1,3-dihydro-3-hydroxy-2H-1,4-benz Piandiazepine-2-one is ...

AI Technical Summary

Problems solved by technology

At present, there are not many reports on the synthesis of this intermediate. The existing synthesis methods have high requirements for equipment, cumbersome post-treatment processes, high raw material costs, and low product yields.

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