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Method for producing 4-fluoro-3-(trifluoromethylsulfonyl)benzenesulfonamide

A technology of trifluoromethanesulfonyl and benzenesulfonamide, applied in chemical instruments and methods, preparation of organic compounds, organic chemistry, etc., can solve problems such as high price of trifluoroiodomethane, harsh reaction conditions, and low reaction yield , to achieve broad commercial application prospects, mild and controllable reaction conditions, and high reaction yield

Inactive Publication Date: 2019-06-07
TIANJIN MODERN VOCATIONAL TECH COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the trifluoromethylation reaction, the trifluoroiodomethane used is expensive, which may cause higher production costs, and it is inconvenient to use and store as a gas at room temperature
[0007] Due to the shortcomings of expensive reagents, harsh reaction conditions and low reaction yields in the methods reported in the existing literature, it is urgent to develop a high-efficiency, low-cost, practical synthetic method for the large-scale preparation of compound 4-fluoro-3-( Trifluoromethanesulfonyl)benzenesulfonamide

Method used

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  • Method for producing 4-fluoro-3-(trifluoromethylsulfonyl)benzenesulfonamide
  • Method for producing 4-fluoro-3-(trifluoromethylsulfonyl)benzenesulfonamide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Synthesis of step (1) compound (II)

[0036] After mixing 2-nitroaniline (250g, 1.81mol) with concentrated hydrochloric acid (450mL) and water (365mL), add sodium nitrite (125g, 1.81mol) and water (300 mL) dropwise to the above solution at 0°C ) mixed solution. After the dropwise addition was completed, stirring was continued for 1 h. Subsequently, a mixed solution of sodium fluoroborate (505 g, 4.6 mol) and water (900 mL) was continuously added dropwise at this temperature, and stirred for 1 h after the dropwise addition was completed. The obtained solution was filtered, and the filter cake was washed three times with ice water (100 g) and methanol (100 mL), respectively, and 363 g of yellow solid II were obtained after drying, with a yield of 85%.

[0037] Synthesis of step (2) compound (III)

[0038] Sodium trifluoromethanesulfinate (396 g, 2.53 mol), cuprous oxide (12 g, 0.08 mol) and DMSO (4 L) were successively added into the three-necked flask. When the tempe...

Embodiment 2

[0046] Step (1) is the same as step (1) in embodiment 1

[0047] Synthesis of step (2) compound (III)

[0048] Sodium trifluoromethylsulfinate (3.96 g, 25.3 mmol), cuprous thiophene-2-carboxylate (CuTC) (160 mg, 0.84 mmol) and DMF (40 mL) were sequentially added into the three-necked flask. When the temperature of the reaction solution was lowered to 15° C., diazonium salt compound II (2 g, 8.4 mmol) was added in batches. After continuing to react for 4 hours, the reaction solution was poured into ice water (80 g), extracted with dichloromethane, the organic phase was washed with water, washed with brine, dried over sodium sulfate, concentrated under reduced pressure and then subjected to column chromatography to obtain 835 mg of light yellow solid III. Yield 39%. 1 The H NMR data is consistent with step (2) in Example 1.

[0049] Synthesis of step (3) compound (IV)

[0050] Compound III (1.55 g, 6.1 mmol), KF (887.4 mg, 15.3 mmol) and DMSO (15 mL) were mixed and stirred a...

Embodiment 3

[0053] Step (1) is the same as step (1) in embodiment 1

[0054] Synthesis of step (2) compound (III)

[0055] Add sodium trifluoromethanesulfinate (3.96g, 25.3mmol), CuBF successively into the three-necked flask 4 (160 mg, 0.84 mmol) and DMSO (50 mL). When the temperature of the reaction solution was raised to 60° C., diazonium salt compound II (2 g, 8.4 mmol) was added in batches. After continuing to react for 4 hours, the reaction solution was poured into ice water (100 g), added dichloromethane for extraction, the organic phase was washed with water, washed with salt water, dried over sodium sulfate, concentrated under reduced pressure and then subjected to column chromatography to obtain 386 mg of light yellow solid III, Yield 18%. 1 The H NMR data is consistent with step (2) in Example 1.

[0056] Synthesis of step (3) compound (IV)

[0057] Compound III (1.55 g, 6.1 mmol), CsF (2.32 g, 15.3 mmol) and DMF (15 mL) were mixed and stirred at 100°C. The reaction was c...

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Abstract

The invention provides a method for producing 4-fluoro-3-(trifluoromethylsulfonyl)benzenesulfonamide. 2-nitroaniline is used as an initial raw material, is subjected to diazotization reaction, trifluoromethyl sulfonation reaction, fluoronation, chlorosulfonation reaction, and is reacted with ammonium hydroxide to finally produce the 4-fluoro-3-(trifluoromethylsulfonyl)benzenesulfonamide. Comparedwith reported synthesis methods, the method for producing the 4-fluoro-3-(trifluoromethylsulfonyl)benzenesulfonamide has the advantages that the reaction yield of the synthesis route is high, used reaction agents are economic and easy to obtain, reaction conditions are mild and controllable, and in a reaction process, column chromatography and purification are not needed, so that the method for producing the 4-fluoro-3-(trifluoromethylsulfonyl)benzenesulfonamide has wide commercial application prospects.

Description

technical field [0001] The invention belongs to the technical field of medicines, and in particular relates to a method for preparing 4-fluoro-3-(trifluoromethanesulfonyl)benzenesulfonamide. Background technique [0002] Apoptosis is an evolutionarily conserved programmed cell death method, and its apoptosis process is very important for the generation, development and drug resistance of tumor cells. Therefore, tumor cells can be inhibited and eliminated by inducing tumor cell apoptosis. Wherein, Navitoclax (ATB-263) is one of potential medicines for the treatment of aging diseases, and the synthesis of Navitoclax (ATB-263) involves the fluoride intermediate 4-fluoro-3-(trifluoromethanesulfonyl)benzenesulfonamide (I ) preparation. [0003] The preparation route of this key intermediate mainly consists of the following types: [0004] (Synthetic Route 1): Using 2-fluorothiophenol as the starting material, trifluoromethylation in the presence of trifluoroiodomethane, and th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C315/04C07C317/14
Inventor 袁文蛟刘雅莉刘鹏牛红军齐菲王静李达王芃孙勇民王立晖褚建伟曲磊
Owner TIANJIN MODERN VOCATIONAL TECH COLLEGE
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