Method for synthesizing cinacalcet hydrochloride intermediate in microchannel reactor

A microchannel reactor, the technology of cinacalcet hydrochloride, is applied in chemical instruments and methods, preparation of organic compounds, preparation of carboxylate, etc. Product purity and yield, the effect of shortening the reaction residence time, reducing the chance of side reactions

Active Publication Date: 2019-10-25
LIVZON GROUP CHANGZHOU KONY PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

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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, wh

Method used

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  • Method for synthesizing cinacalcet hydrochloride intermediate in microchannel reactor
  • Method for synthesizing cinacalcet hydrochloride intermediate in microchannel reactor
  • Method for synthesizing cinacalcet hydrochloride intermediate in microchannel reactor

Examples

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Embodiment 1

[0037] Microchannel reactor 1 in this embodiment includes preheating module 1, preheating module 2, reaction module group 1 and cooling quenching module 1, preheating module 1 and preheating module 2 are arranged in parallel, preheating module 1, preheating module 1 The thermal modules two are connected in series with the reaction module group one, and the other end of the reaction module group one is connected in series with the cooling and quenching module one.

[0038] 1. Put 300g of 3-(3-trifluoromethylphenyl)-2-acrylic acid into 2L of organic solvent A, stir to form a white suspension slurry, wherein organic solvent A is toluene;

[0039] 2. Weigh 9g of palladium carbon (palladium accounts for 5% of the total mass of the catalyst), add it to the white slurry and stir thoroughly to obtain the mixture as material a;

[0040] 3. Use material pump A to transport material a to preheating module 1 at 35g / min for preheating;

[0041] 4. Control the flow meter B to transport the...

Embodiment 2

[0045] This example differs from Example 1 in that: the solvent A in Step 1 of this example is xylene, and the purity of the material in the filtered filtrate is 99.25% (GC).

Embodiment 3

[0047]The difference between this example and Example 1 is that the solvent A in step 1 of this example is tetrahydrofuran, the reaction pressure in step 5 is 1.0 Mpa, and the purity of the material in the filtered filtrate is 99.13% (GC).

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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...

Claims

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Application Information

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IPC IPC(8): C07C51/36C07C57/58C07C51/60C07C57/76
CPCC07C51/36C07C51/60C07C57/58C07C57/76
Inventor 张之建陈争一潘亮张策文殷波王建曹丽
Owner LIVZON GROUP CHANGZHOU KONY PHARMA
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