Synthesis method of 4-cyano-3-(trifluoromethyl)benzene-1-sulfonyl chloride

Abstract

The invention relates to the field of organic synthesis, and discloses a synthesis method of 4-cyano-3-(trifluoromethyl)benzene-1-sulfonyl chloride. The method includes the following steps that cuprous chloride is added into water, thionyl chloride is dropped into an ice-water bath and placed at room temperature for 8-12 hours, and a solution a is obtained; acid is added into 4-amino-2-(trifluoromethyl)benzonitrile ice-water bath, a sodium nitrite aqueous solution is dropped at 0-5 DEG C and stirred for 30-60 min, an organic solvent a is added for promoting solubilization, then the solution isstirred for 20-40 min at 0-5 DEG C, and a reaction liquid a is obtained; the reaction liquid a is dropped into the solution a by using the organic solvent a for promoting solubilization, reaction lasts for 0.5-2 hours at 0-35 DEG C, then water washing, extraction with an organic solvent b and purification are conducted in sequence, and 4-cyano-3-(trifluoromethyl)benzene-1-sulfonyl chloride is obtained. The synthesis method has the advantages that the raw materials are easy to obtain, the reaction condition is mild, the selectivity is high, the yield is about 85%, the process is simple, the cost is low and large-scale production can be achieved.

Description

technical field [0001] The invention belongs to the field of organic medicine synthesis, and specifically relates to a synthesis method of 4-cyano-3-(trifluoromethyl)benzene-1-sulfonyl chloride, which is used as a medicine intermediate for inhibiting the transient receptor potential A1 ion channel. Background technique [0002] At present, 4-cyano-3-(trifluoromethyl)benzene-1-sulfonyl chloride, as a pharmaceutical intermediate for inhibiting the transient receptor potential A1 ion channel, can be used to synthesize and prepare drugs or inhibitors for the treatment of inflammatory airway diseases . In the prior art, 4-cyano-3-(trifluoromethyl)benzene-1-sulfonyl chloride generally adopts the following synthetic route: [0003] [0004] The yield of this method is generally 50% to 60%, but the synthesis methods all need to use sulfur dioxide, which has a stimulating effect on the respiratory tract, can cause bronchospasm, irritate the eyes, and have an unpleasant taste. The...

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Problems solved by technology

[0004] The yield of this method is generally 50% to 60%, but the synthesis methods all need to use sulfur dioxide, which has a stimulating effect on the respiratory tract, can cause bronchospasm, irritate the eyes, and have an unpleasant taste. The amount of waste liquid is increased during processing, which pollutes the environment and is not harmful. Facilitate the scale-up of production

It can be seen that in the prior art about the synthetic method of 4-cyano-3-(trifluoromethyl)benzene-1-sulfonyl chloride, due to the relatively high risk, environmental pollution and other reasons make the compound difficult to scale up production

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