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Preparation method of m-trifluoromethyl phenylpropionic acid

A technology of trifluoromethylphenylpropionic acid and trifluoromethylbutanoic acid, which is applied in the field of m-trifluoromethylphenylpropionic acid preparation, can solve the problem of difficult to purify cinacalcet impurities, which are difficult to remove and affect the quality of finished products, etc. question

Active Publication Date: 2018-04-27
CHANGZHOU SUNLIGHT PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Document 2 suggests that there is a risk of the benzene ring being hydrogenated and reduced in the catalytic hydrogenation reaction, and the benzene ring reduction impurities (see compounds A to C below) do not have UV absorption characteristics, making it difficult to use UV light in m-trifluoromethylphenylpropionic acid. The detector detects it, so that it will participate in the subsequent steps of the preparation of cinacalcet hydrochloride along with m-trifluoromethylphenylpropionic acid, and finally form cinacalcet impurities that are difficult to purify, affecting the quality of the finished product
[0008] Document 3 discloses that the use of sodium hydroxide can effectively avoid the risk of hydrogenation reduction of the benzene ring, but it is suggested that this will produce the defluorinated impurity m-methylphenylpropionic acid (see compound D below), which is also difficult to obtain from m-trifluoromethyl Phenylpropionic acid is removed, and then along with m-trifluoromethylphenylpropionic acid, it will also participate in the subsequent steps of the cinacalcet hydrochloride preparation process, and eventually remain in the finished product to affect its quality

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1）

[0028] The preparation method of the m-trifluoromethylphenylpropionic acid of the present embodiment is as follows:

[0029] 216.0 g of m-trifluoromethylcinnamic acid (1.0 mol), 1 L of water, and 53.0 g of sodium carbonate (0.5 mol) were added to a 2 L four-neck flask, stirred and dissolved, and then transferred to a hydrogenation kettle.

[0030] Then add 10g, 3wt% palladium-carbon catalyst to the hydrogenation kettle, and after nitrogen replacement, hydrogen gas is introduced, and the temperature is maintained at 25±5°C and the pressure is 0.2-0.3MPa for 3 hours.

[0031] After the reaction, filter, and adjust the pH of the filtrate to 3-4 with 2N dilute hydrochloric acid, a white solid precipitates, then add 1L of toluene to extract once, separate the layers, wash the organic layer with 1L of water once, separate the layers, combine the organic layers, and Concentrate under reduced pressure at a temperature of 55±5°C to obtain a colorless transparent oil, and finally cool n...

Embodiment 2～ Embodiment 4）

[0034] The method of each embodiment is substantially the same as Example 1, except that the sodium carbonate consumption is specifically shown in Table 1.

[0035] Table 1

[0036]

Embodiment 5

[0038] The method of embodiment 5 and embodiment 6 is substantially the same as embodiment 1, and difference is sodium carbonate consumption, specifically see table 2.

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PUM

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Abstract

The invention discloses a preparation method of m-trifluoromethyl phenylpropionic acid, which is prepared through catalytic hydrogenation of m-trifluoromethyl cinnamic acid. The catalytic hydrogenation is carried out in the presence of a strong-alkali and weak-acid salt, molar ratio of the strong-alkali and weak-acid salt to the m-trifluoromethyl cinnamic acid being 0.2:1-0.9:1. The strong-alkaliand weak-acid salt preferably is Na2CO3 or K2CO3. In the catalytic hydrogenation of m-trifluoromethyl cinnamic acid, the Na2CO3 or K2CO3 is added according to certain molar ratio, so that generation of benzene ring reduction impurities A, B and C and defluorination impurity D is prevented effectively at the same time, thereby producing the m-trifluoromethyl phenylpropionic acid at high purity, further synthesizing high-purity cinacalcet hydrochloride.

Description

technical field [0001] The invention belongs to the technical field of medicine and chemical industry, and in particular relates to a preparation method of m-trifluoromethylphenylpropionic acid. Background technique [0002] Cinacalcet hydrochloride is a calcimimetics developed by NPS Pharmaceuticals in the United States. It activates the calcium receptors in the parathyroid glands, thereby reducing the secretion of parathyroid hormone (PTH), regulates the behavior of the calcium receptors in the parathyroid glands, and reduces the thyroid gland by enhancing the sensitivity of the receptors to calcium levels in the blood stream. Levels of parathyroid hormone, calcium, phosphorus, and calcium-phosphorus complex. It is mainly used for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on dialysis and hypercalcemia in patients with parathyroid carcinoma. [0003] m-trifluoromethyl phenylpropionic acid is an important raw material for ...

Claims

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Application Information

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IPC IPC(8): C07C51/36C07C57/58
CPCC07C51/36C07C57/58
Inventor 胡国宜胡锦平李喜龙高永清鲁炜奚小金
Owner CHANGZHOU SUNLIGHT PHARMA
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