Method for preparing 5-methoxy-1-(4-trifluoromethyl phenyl)pentanone

A technology of trifluoromethylphenyl and trifluoromethylbenzoic acid is applied in the field of preparation of 5-methoxy-1-(4-trifluoromethylphenyl)pentanone, which can solve the problem of environmental pollution, The actual yield is low, the volatility is strong, etc., and the production process is pollution-free, the reaction cycle is short, and the environment is friendly.

Inactive Publication Date: 2008-03-05
NORTHWEST NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The main shortcoming of this method is: (1) p-trifluoromethylbenzene cyanide toxicity is stronger as starting material, and its production and use can pollute the environment; (2) 1-halogen-4-methoxybutane Volatility is stronger, and loss is serious under this condition, and the actual yield of product is relatively low, only 60-65%; (3) reaction cycle is long, and efficiency is low

Method used

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  • Method for preparing 5-methoxy-1-(4-trifluoromethyl phenyl)pentanone
  • Method for preparing 5-methoxy-1-(4-trifluoromethyl phenyl)pentanone
  • Method for preparing 5-methoxy-1-(4-trifluoromethyl phenyl)pentanone

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Experimental program
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Embodiment 1

[0034] step one

[0035]

[0036] In a 50mL round-bottomed flask, add p-trifluoromethylbenzoic acid (3.81g, 20mmol), thionyl chloride (4.5g, 38mmol) and 1 drop of dimethylformamide, reflux under stirring, and wash with 40% NaOH solution Absorb the sulfur dioxide and hydrogen chloride gas produced by the reaction, and react until no gas is released. Excess thionyl chloride was recovered by distillation, and the remaining mixture was distilled under reduced pressure to collect fractions at 85-90° C. (16 mmHg) to obtain p-trifluoromethylbenzoyl chloride (3.90 g) as a colorless liquid with a yield of 93%.

[0037] step two

[0038]

[0039] Add anhydrous methanol (30mL, 0.75mol) and anhydrous tetrahydrofuran (60mL, 0.75mol) into a 250mL dry three-necked flask equipped with a condenser tube, a drying tube and a constant pressure funnel, and add thionyl chloride dropwise under cooling in an ice bath, Added within 1h.. After the addition, it was heated to reflux at 100°C for...

Embodiment 2

[0047] step one

[0048]

[0049] In a 50mL round-bottomed flask, add p-trifluoromethylbenzoic acid (3.81g, 20mmol), thionyl chloride (4.5g, 38.0mmol) and 1 drop of dimethylformamide, reflux under stirring, and The sodium solution absorbs the generated gas until the sulfur dioxide and hydrogen chloride gas disappear. Distill off the excess thionyl chloride, then distill the remaining mixture, collect 85-90 °C / 16mmHg, and obtain a colorless liquid p-trifluoromethylbenzoyl chloride (3.80g ), the yield is 91%.

[0050] step two

[0051]

[0052] Add 1,4-dibromobutane (21.5 g, 0.1 mol) and anhydrous methanol (10 ml) into a dry three-necked flask equipped with a condenser tube, a drying tube and a constant pressure funnel, stir to make it evenly mixed, and heat to After 70°C, a methanol solution of sodium methoxide (5.4 g of sodium methoxide, 30 mL of anhydrous methanol) was added dropwise. After the addition, reflux for 2 hours. After the reaction liquid is cooled, filter t...

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Abstract

The present invention discloses process of preparing 5-methoxyl-1-(4-trifluoromehyl phenyl) pentanone as one key intermediate for preparing depression treating medicine fluvoxamine maleate with p-trifluoromethyl benzoyl chloride and magnesium 4-methoxyl butyl halide in the presence of catalyst. The process includes following four steps: 1. preparing p-trifluoromethyl benzoyl chloride with p-trifluoromethyl benzoic acid and thionyl chloride through chlorination; 2. preparing 1-halo-4-methoxyl butane; 3. preparing Grignard reagent through reaction of 1-halo-4-methoxyl butane and metal Mg; and 4. preparing 5-methoxyl-1-(4-trifluoromehyl phenyl) pentanone through reaction of p-trifluoromethyl benzoyl chloride and the Grignard reagent. The process has the features of facile material, low cost, short reaction period, high efficiency and environment friendship.

Description

technical field [0001] The invention relates to a preparation method of 5-methoxyl-1-(4-trifluoromethylphenyl)pentanone, a key intermediate for producing fluvoxamine maleate. Background technique [0002] 5-Methoxy-1-(4-trifluoromethylphenyl)pentanone is a key intermediate in the production of fluvoxamine maleate, which is widely used in European and American countries It is a highly effective drug for treating obsessive-compulsive disorder and depression. In 2000, the drug was listed among the top 200 best-selling drugs in the world. At present, the preparation of 5-methoxy-1-(4-trifluoromethylphenyl)pentanone usually adopts the following method: with 1-halogen-4-methoxybutane and p-trifluoromethylbenzene cyanide as basic Raw material, the former is firstly made into Grignard reagent in ether or THF, then undergoes addition reaction with the latter, and finally acidified and hydrolyzed to obtain 5-methoxy-1-(4-trifluoromethylphenyl)pentanone. Its synthetic route is as fol...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C49/84C07C45/41
Inventor 胡雨来王建林杨磊吴江林
Owner NORTHWEST NORMAL UNIVERSITY
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