A kind of preparation method of 4-methanesulfonylacetophenone and α-bromo-4-methanesulfonylacetophenone

Abstract

The invention discloses a preparation method of 4-(methylsulfonyl)phenyl]-1-ethanone and alpha-bromo-4-(methylsulfonyl)phenyl]-1-ethanone. Preparation of the 4-(methylsulfonyl)phenyl]-1-ethanone comprises the steps of reacting 4-iodoacetophenone and mesylate in a solvent in the copresence of inorganic base, a catalyst and alkenyl quaternary ammonium salt to generate the 4-(methylsulfonyl)phenyl]-1-ethanone; and preparation of the alpha-bromo-4-(methylsulfonyl)phenyl]-1-ethanone comprises the steps of reacting the prepared 4-(methylsulfonyl)phenyl]-1-ethanone and bromine in a solvent at the temperature of 30-40 DEG C to obtain the final product. By the preparation method, perfect product yield can be obtained, waste gas, waste water and solid wastes are less, and the preparation method is suitable for industrialized large-scale production.

Description

technical field [0001] The invention belongs to the field of drug synthesis, in particular to an intermediate of rofecoxib or erecoxib, in particular to a preparation of 4-methylsulfonyl acetophenone and α-bromo-4-methylsulfonyl acetophenone Preparation. Background technique [0002] α-Bromo-4-methylsulfonylacetophenone is an important intermediate of a new generation of anti-inflammatory drugs - type 2 cyclooxygenase inhibitor rofecoxib, and is also an important intermediate of Erecoxib - a non-steroidal anti-inflammatory analgesic ( NSAIDs) important intermediates, its structural formula is as follows: [0003] [0004] At present, there are roughly two ways for the synthetic route of 4-methylsulfonyl acetophenone and / or α-bromo-4-methylsulfonyl acetophenone, the first oxidation route (such as the 3rd phase of synthetic chemistry, Vol .12, 2004, 290-292, Zhang Shiying et al.: Synthesis of α-bromo-4-methylsulfonylacetophenone): [0005] [0006] However, in the abo...

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[0011] Another example is the document 'Organic Chemistry Communications, 2002, vol.4, #25, p.4423-4425', which discloses the same route, and the reaction conditions are in the combination of cuprous benzene trifluoromethanesulfonate and N,N' In the presence of -dimethylethylenediamine, 4-methylsulfonyl acetophenone is prepared by reacting with sodium methanesulfonate in dimethyl sulfoxide, and the yield is only about 80%; the reactions of the above two documents are simultaneously Reaction in high-boiling polar solvent dimethyl sulfoxide, which is easy to decompose and miscible with water, difficult to recycle, waste resources and increase the difficulty of later sewage treatment

[0012] Another example is Chemical Communications (Chemical Communications), 2012, vol.48, #60, p.7513-7515, which discloses that the conditions of the first step reaction are in the presence of cuprous oxide and potassium tert-butoxide, in an aerobic environment Reacting with dimethyl sulfoxide in acetylacetone to prepare 4-methylsulfonylacetophenone, the yield is only about 52%, which is not conducive to large-scale production;

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