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Preparation method of 6-chloro-4-trifluoromethyl-3-cyanopyridine

A technology of trifluoromethyl and cyanopyridine, applied in the field of preparation of 6-chloro-4-trifluoromethyl-3-cyanopyridine, can solve the problems of complicated operation, poor environmental protection, low yield and the like, and achieves The effect of high yield and purity, less by-products, and less side reactions

Active Publication Date: 2022-01-11
XINFA PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

To solve the problems of high price of 6-chloro-4-trifluoromethyl-3-cyanopyridine prepared in the prior art, difficult acquisition of raw materials, poor environmental protection, cumbersome operation, low yield and difficulty in industrialization promotion

Method used

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  • Preparation method of 6-chloro-4-trifluoromethyl-3-cyanopyridine
  • Preparation method of 6-chloro-4-trifluoromethyl-3-cyanopyridine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1: Preparation of 6-hydroxyl-4-trifluoromethyl-3-cyanopyridine (Ⅵ)

[0054] In the 250 milliliter four-necked flask that is connected with stirring, thermometer, reflux condenser, add 18.9 grams (0.1 moles) 2-chloro-3-trifluoromethyl methacrylate, 10.5 grams (0.1 moles) 2-chloro-3 -Aminopropionitrile, 0.04 g of DBU, stirred and reacted between 20 and 25°C for 3 hours, the addition reaction was detected by GC and transferred to a constant pressure dropping funnel for use. Add 100 g of toluene to a 500 ml four-neck flask connected with a stirring, thermometer, reflux condenser and constant pressure dropping funnel, heat, and add the obtained addition product dropwise at 90 to 95 ° C, dropwise for 2 hours After that, react at 90 to 95°C for 2 hours, cool, add 34.5 grams of potassium carbonate between 20 and 25°C, stir and react for 3 hours between 20 and 25°C, pour the reactant into 100 grams of water, and acidify with 30% hydrochloric acid The pH value of the sys...

Embodiment 2

[0058] Example 2: Preparation of 6-hydroxyl-4-trifluoromethyl-3-cyanopyridine (Ⅵ)

[0059] In a 500 ml four-necked flask connected with stirring, a thermometer, and a reflux condenser, add 101.3 grams (0.5 moles) of 2-chloro-3-trifluoroethyl methacrylate, 53.0 grams (0.51 moles) of 2-chloro-3 -Aminopropionitrile, 0.5 g of DBU, stirred and reacted at 20-25°C for 3 hours, the addition reaction was detected by GC and transferred to a constant pressure dropping funnel for use. Add 400 g of toluene to a 1000 ml four-neck flask connected with a stirring, thermometer, reflux condenser and constant pressure dropping funnel, heat, and add the obtained addition product dropwise at 90 to 95 ° C, dropwise for 2 hours After that, react at 90 to 95°C for 2 hours, cool, add 45 grams of sodium hydroxide between 20 and 25°C, stir and react for 3 hours between 20 and 25°C, pour the reactant into 200 grams of water, and wash with 30% hydrochloric acid The pH value of the acidification system wa...

Embodiment 3

[0060] Embodiment 3: Preparation of 6-chloro-4-trifluoromethyl-3-cyanopyridine (I)

[0061] Add 150 grams of 1,2-dichloroethane, 18.8 grams (0.1 moles) of 6-hydroxyl-4-trifluoromethane prepared in Example 1 to a 500-milliliter four-necked flask equipped with a thermometer, mechanical stirring, and a reflux condenser. Base-3-cyanopyridine, 26.0 grams (0.125 moles) phosphorus pentachloride, 90-95 ℃ stirred and reacted for 10 hours, then slowly reactant was poured into 100 grams of ice water, fully stirred, then with 40wt% hydroxide Sodium aqueous solution neutralizes the pH value to 7-8, separates the layers, extracts the aqueous layer three times with 1,2-dichloroethane, 50 grams each time, combines the organic phases, washes with 30 grams of saturated saline, and then washes them with 5 grams of anhydrous Dry over sodium sulfate, and remove the solvent by rotary evaporation to obtain 19.4 g of 6-chloro-4-trifluoromethyl-3-cyanopyridine (I), with a yield of 93.9% and a gas phas...

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Abstract

The invention provides a preparation method of 6-chloro-4-trifluoromethyl-3-cyanopyridine, which comprises the following steps: by taking 2-chloro-3-trifluoromethyl acrylate (II) and 2-chloro-3-aminopropionitrile (III) as raw materials, carrying out addition reaction to obtain 2,4-dichloro-3-trifluoromethyl-4-cyano-5-amino valerate (IV), carrying out molecular lactamization reaction to obtain 3,5-dichloro-4-trifluoromethyl-5-cyano piperidine-2-one (V), then removing hydrogen chloride to obtain 6-hydroxy-4-trifluoromethyl-3-cyanopyridine (VI), and then carrying out chlorination reaction on VI and a chlorination reagent to obtain 6-chloro-4-trifluoromethyl-3-cyanopyridine (I). The raw materials used in the invention are cheap and easily available; the preparation and operation method is simple, small in wastewater amount, safe, environment-friendly and low in cost; the method has the advantages of high reaction selectivity, few byproducts and high target product yield and purity, and is suitable for green industrial production.

Description

technical field [0001] The invention relates to a preparation method of 6-chloro-4-trifluoromethyl-3-cyanopyridine, which belongs to the technical field of fine chemistry and chemical industry. Background technique [0002] 6-Chloro-4-trifluoromethyl-3-cyanopyridine (I) is an important intermediate, which can be used to develop new medicines and pesticides, research and optimize 6-chloro-4-trifluoromethyl-3-cyano The preparation method of pyridine is of great significance for the development of its downstream products. [0003] The world patent PCT2009152133 uses 6-chloro-4-trifluoromethylpyridine-3-carboxylic acid as a raw material to obtain 6-chloro-4-trifluoromethylpyridine-3-carboxamide through amidation reaction, and then reacts with phosphorus oxychloride Dehydration gave 6-chloro-4-trifluoromethyl-3-cyanopyridine with a total yield of 73.1%. The reaction process is described as the following reaction scheme 1. [0004] [0005] The raw material 6-chloro-4-trifluo...

Claims

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Application Information

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IPC IPC(8): C07D213/85
CPCC07D213/85Y02P20/55
Inventor 钱余峰戚聿新吕强三
Owner XINFA PHARMA
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