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Preparation method for 3-(trifluoromethyl)benzenepropanol

A technology of trifluoromethyl phenylpropanol and trifluoromethyl phenylpropanoic acid, applied in the field of preparation of m-trifluoromethyl phenylpropanol, can solve the problems of combustion, explosion, complex synthesis route, high toxicity of borane and the like , to achieve the effect of mild reaction conditions, simple post-processing and simple operation

Active Publication Date: 2015-09-09
CHANGZHOU SUNLIGHT PHARMA
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  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The disadvantage of this type of method is that it needs to use a catalyst with a higher price, which leads to higher production costs and is not suitable for large-scale industrial production.
The disadvantages of this method are: the raw materials are not easy to obtain, improper handling of the format reaction will cause combustion and explosion, and the safety is poor, so it is not suitable for industrialized large-scale production
The disadvantage of this method is that the synthesis route is complicated, and the conditions of selective hydrogenation and catalytic hydrogenation are relatively harsh.
The former method is not suitable for large-scale industrial production because Lithium tetrahydrogen is prone to combustion and explosion when it encounters water, damp or improper post-treatment, and has extremely poor safety.
The latter method is also not suitable for large-scale industrial production due to the high toxicity and spontaneous combustion characteristics of borane

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1）

[0024] The preparation method of the m-trifluoromethyl phenylpropanol of the present embodiment is as follows:

[0025] First add 54.5g of m-trifluoromethylphenylpropionic acid (0.25mol) and 270mL of anhydrous tetrahydrofuran into a four-neck flask, cool to 2°C±2°C in an ice-water bath; then add in batches while stirring (the temperature is controlled at Below 10°C) 23.8g of sodium borohydride (0.625mol), continue to stir for 10min; then slowly add dropwise (temperature controlled below 10°C) 24.0g of methanesulfonic acid (0.25mol), add about 30min, and finally Slowly raise the temperature to room temperature (20°C±2°C), react for 3 hours, and stop the reaction after the control disappears in the sampling center.

[0026] After the reaction, add 380mL of water dropwise, stir for 30min, distill THF off, then add 190mL of ethyl acetate, stir, and separate the liquids. The organic phase (upper layer) is dried with anhydrous sodium sulfate, concentrated, and distilled under reduce...

Embodiment 2～ Embodiment 4）

[0028] Each embodiment is basically the same as Embodiment 1, and the differences are shown in Table 1.

[0029] Table 1

[0030] Example 1 Example 2 Example 3 Example 4 Lewis acid Methanesulfonic acid 24.0g Concentrated sulfuric acid 25.0g Trifluoroacetic acid 28.5g Anhydrous zinc chloride 34.0g m-trifluoromethyl phenylpropanol 48.8g 46.8g 46.0g 47.0g yield 95.1% 90.8% 89.5% 91.3% purity 99.4% 98.9% 99.2% 99.1%

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Abstract

The invention discloses a preparation method for 3-(trifluoromethyl)benzenepropanol. According to the method, in an inert solvent, 3-(trifluoromethyl)hydrocinnamic acid is reduced to generate 3-(trifluoromethyl)benzenepropanol under the presence of boron hydride as a reducing agent and Lewis acid as a cocatalyst. The inert solvent is composed of one or two components selected from methyl tert-butyl ether, isopropyl ether, methyl tetrahydrofuran and tetrahydrofuran. The molar ratio of boron hydride to 3-(trifluoromethyl)hydrocinnamic acid is 1:1 to 3:1. The boron hydride is in the form of sodium borohydride, potassium borohydride, lithium borohydride or zinc borohydride. The molar ratio of Lewis acid to 3-(trifluoromethyl)hydrocinnamic acid is 1:1 to 2:1. The Lewis acid is in the form of methanesulfonic acid, concentrated sulfuric acid, trifluoroacetic acid, zinc chloride, aluminium trichloride or zirconium chloride. The method is mild in reaction condition, simple in operation and post-treatment, and especially high in safety, thus being suitable for industrial mass production.

Description

technical field [0001] The invention belongs to the technical field of preparation of pharmaceutical intermediates, and in particular relates to a preparation method of m-trifluoromethyl phenylpropanol. 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] The chemical name of cinacalcet hydrochloride is: (R)-N-(1-(naph...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C29/147C07C33/46
CPCC07C29/147C07C33/46
Inventor 胡锦平胡国宜郑建龙李宏成王永成
Owner CHANGZHOU SUNLIGHT PHARMA
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