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

A kind of technology of methanesulfonyl acetophenone and acetophenone, applied in the preparation of 4-methanesulfonyl acetophenone and α-bromo-4-methanesulfonyl acetophenone, rofecoxib or erecoxib In the field of intermediates, it can solve the problems of waste of resources, easy miscibility, easy decomposition, etc., and achieve the effect of reducing sewage discharge, complying with environmental protection, high product yield and purity

A kind of technology of methanesulfonyl acetophenone and acetophenone, applied in the preparation of 4-methanesulfonyl acetophenone and α-bromo-4-methanesulfonyl acetophenone, rofecoxib or erecoxib In the field of intermediates, it can solve the problems of waste of resources, easy miscibility, easy decomposition, etc., and achieve the effect of reducing sewage discharge, complying with environmental protection, high product yield and purity

CN109134318BActive Publication Date: 2020-04-17江苏美迪克化学品有限公司
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  • A kind of preparation method of 4-methanesulfonylacetophenone and α-bromo-4-methanesulfonylacetophenone
  • A kind of preparation method of 4-methanesulfonylacetophenone and α-bromo-4-methanesulfonylacetophenone
  • A kind of preparation method of 4-methanesulfonylacetophenone and α-bromo-4-methanesulfonylacetophenone

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Embodiment 1 prepares 4-methylsulfonyl acetophenone

[0047] The route is as follows:

[0048]

example 1-1

[0050] 4-iodoacetophenone (24.6g), sodium methanesulfonate (15.3g), N,N-dimethyl-N-[2-(methacryloyloxy)ethyl]-1-butan Ammonium bromide (2.9g, formula I-5), potassium carbonate (20.7g) and cuprous iodide (1.9g) were added to 500ml of toluene, and heated to 110±2°C under nitrogen protection for 24 hours. After the reaction was completed, the reaction solvent was recovered by concentrating under reduced pressure. Add water and dichloromethane to dissolve, add activated carbon to absorb and decolorize, filter with a small amount of diatomaceous earth, separate layers, dry the dichloromethane layer with anhydrous sodium sulfate, concentrate to dryness, add ethanol for beating, filter, and dry to obtain 4- Methylsulfonyl acetophenone 18.1g, yield 91.3%, purity 98.2%.

example 1-2

[0052] 4-iodoacetophenone (24.6g), sodium methanesulfonate (20.4g), N,N-dimethyl-N-[2-(methacryloyloxy)ethyl]-1-benzyl Ammonium bromide (3.3g, formula I-1), cesium carbonate (65.1g) and cuprous iodide (1.9g) were added to 500ml of chlorobenzene, and heated to 110±2°C under nitrogen protection for 24 hours. After the reaction was completed, the reaction solvent was recovered by concentrating under reduced pressure. Add water and dichloromethane to dissolve, add activated carbon to absorb and decolorize, and filter with a small amount of diatomaceous earth. The layers were separated, and the dichloromethane layer was dried over anhydrous sodium sulfate and concentrated to dryness. Add ethanol for beating, filter and dry to obtain 18.8 g of 4-methylsulfonylacetophenone with a yield of 94.9% and a purity of 98.4%.

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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...

Claims

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Application Information

Patent Timeline
17 Apr 2020
Publication
CN109134318B
IPC
C07C315/00; C07C317/24
CPC
C07C315/00; C07C317/24
Inventors
杨盟; 徐肖洁