Method for synthesizing cinacalcet hydrochloride intermediate in microchannel reactor

Abstract

The invention provides a method for synthesizing cinacalcet hydrochloride intermediate in a microchannel reactor. The method comprises the steps that 3-(3-trifluoromethylphenyl)-2-acrylic acid and a supported noble metal catalyst are added into an organic solvent A to react with hydrogen to generate 3-(3-trifluoromethylphenyl)propionic acid; after the reaction, filtration is conducted, and a catalyst B and thionyl chloride are added into filtrate to react to generate 3-(3-trifluoromethylphenyl)propionyl chloride, and the two intermediates are all finished in the microchannel reactor. By usingefficient mass transfer and heat transfer of the microchannel reactor, time of hydrogenation is effectively shortened, generation of esterification by-products in the hydrogenation process is prevented, the purity and yield of products are improved, palladium carbon is recovered and applied ,mechanically for many times, cumbersome operation in the kettle reaction process is overcome, and at the same time, materials generated in the reaction can be directly used for the next reaction; and the usage amount of the thionyl chloride in the preparation process of acyl chloride is reduced, waste discharge is reduced, and a green process for synthesizing cinacalcet hydrochloride intermediate is provided.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a method for synthesizing a cinacalcet hydrochloride intermediate in a microchannel reactor. Background technique [0002] Hypercalcemia refers to an abnormal increase in the concentration of ionized calcium in the serum, which is generally caused by diseases such as primary hyperparathyroidism, renal failure, hyperthyroidism, etc. Hypercalcemia not only causes respiratory, digestive, cardiovascular , neuromuscular and other system disorders, and also cause damage to renal function, which can be life-threatening in severe cases; Cinacalcet hydrochloride (Cinacalcet hydrochloride) trade name: Cinacalcet, chemical name: N-( (1R)-1-(1-naphthyl)ethyl)-3-(3-(trifluoromethyl)phenyl)propan-1-amine. [0003] 3-(3-trifluoromethylphenyl)propionyl chloride is the key intermediate for the preparation of cinacalcet hydrochloride, and 3-(3- Trifluoromethylphenyl) propionic acid, then...

AI Technical Summary

Problems solved by technology

[0013] In the above process of preparing 3-(3-trifluoromethylphenyl)propionic acid, the reducing agent is hydrogen and the consumption is large, and it needs to be operated under high pressure, and the operation is cumbersome and has great potential safety hazards; Chemical by-products are produced, and residual alcohol has a great impact on the next step of synthesizing 3-(3-trifluoromethylphenyl) propionyl chloride, which needs to be guaranteed by post-processing, and post-processing is cumbersome; while preparing 3-( In the process of 3-trifluoromethylphenyl) propionyl chloride, the consumption of thionyl chloride is large, the demand for solvent is also large, the amount of waste discharge is large, the environment is seriously polluted, and the yield is low, and there is a danger of potential safety hazards in large-scale production

Images