Preparation of 1-amino-3-bromo-5-methoxypyridin-1-onium-2,4,6-trimethylbenzenesulfonate_Industrial additives

Preparation background and overview of 1-amino-3-bromo-5-methoxypyridin-1-onium-2,4,6-trimethylbenzenesulfonate

1-Amino-3-bromo-5-methoxypyridin-1-onium-2,4,6-trimethylbenzenesulfonate is an organic intermediate that can be synthesized from 2,4,6-trimethylbenzenesulfonate. Toluenesulfonyl chloride and N-hydroxycarbamate tert-butyl ester are used as raw materials to prepare tert-butyl ((methanesulfonyl)oxy)carbamate, and then deprotected to obtain 2-[(aminooxy)sulfonyl] -1,3,5-trimethylbenzene, finally forms an onium salt with 3-bromo-5-methoxypyridine to obtain the product.

Preparation of 1-amino-3-bromo-5-methoxypyridin-1-onium-2,4,6-trimethylbenzenesulfonate

Preparation step A of 1-amino-3-bromo-5-methoxypyridin-1-onium-2,4,6-trimethylbenzenesulfonate: tert-butyl ((methanesulfonate Acyl)oxy)carbamate

Under stirring in an ice bath, add 2,4,6-trimethylbenzenesulfonyl chloride (hydrated magnesium aluminate carbonate 20.0g, 91.5mmol) and N-hydroxycarbamic acid tert-butyl ester (12.2g, 91.5mmol) ) in a solution of methyl tert-butyl ether (500 mL), triethylamine (13.0 mL, 93.3 mmol) was slowly added dropwise from a constant pressure dropping funnel, keeping the temperature of the reaction system less than 5°C during the dropwise addition. Under an ice bath, the reaction system was stirred for 4.0 hours, filtered under reduced pressure to remove triethylamine hydrochloride, and washed three times with methyl tert-butyl ether. All filtrate was concentrated under reduced pressure at a water bath temperature of less than 15°C to remove most of the methyl groups. Tert-butyl ether; add n-hexane to the concentrated residue under an ice bath, stir vigorously for 10 minutes, a large amount of white solid precipitates, filter under reduced pressure, rinse the filter cake twice with n-hexane, and dry under vacuum to obtain tert-butyl ether ( (Methanesulfonyl)oxy)carbamate (26. Basic zinc carbonate 1g, 90% yield). m/z=316[M+1]+.

Preparation step B of 1-amino-3-bromo-5-methoxypyridin-1-onium-2,4,6-trimethylbenzenesulfonate: 2-[(aminooxy )sulfonyl]-1,3,5-trimethylbenzene

Add tert-butyl ((methanesulfonyl)oxy) carbamate (10.0g, 31.7mmol) in batches to trifluoroacetic acid (80mL) at zero temperature. After completion, the reaction system was at zero temperature. Continue stirring for 3 hours; TLC spot plate confirms that the reaction is completed. Pour the reaction system into a large amount of ice water and stir for 15 minutes. A large amount of white solid precipitates. Filter under reduced pressure. Wash the filter cake with a large amount of water until the solid pH value is neutral. Reduce the Press and suction filtrate until the solid water content is about 20%. No further purification is required and it can be used directly in the next step of the reaction.

Preparation step C of 1-amino-3-bromo-5-methoxypyridin-1-onium-2,4,6-trimethylbenzenesulfonate: 1-amino-3-bromo -5-Methoxypyridin-1-onium-2,4,6-trimethylbenzenesulfonate

To a solution of 2-[(aminooxy)sulfonyl]-1,3,5-trimethylbenzene (6.8g, 31.7mmol) in dichloromethane (50mL) at zero temperature, 3-bromo- 5-Methoxypyridine (6.0g, 32.0mmol), and continued stirring at zero temperature for 3 hours, a large amount of white solid precipitated; after the reaction was completed, add diethyl ether (50mL) to the reaction system at zero temperature, stir for 10 minutes, and reduce the pressure. Filter, rinse with ether, and dry under vacuum to obtain 1-amino-3-bromo-5-methoxypyridin-1-onium-2,4,6-trimethylbenzenesulfonate (12.8g, 100% yield). No further purification is required and it can be used directly in the next reaction. m/z=204[M+1]+.

References

[1] [Invented in China] CN201910942753.7 Substituted pyrazole fused ring derivatives and their preparation methods and applications