Sodium hydride → HCID 15342056, compound

Temperature

2.5 °C

A solution of 5-amino-4-bromo-3-methylisoxazole (177 mg, 1.0 mmol) in dry tetrahydrofuran (THF, 2 mL) was added to a suspension of sodium hydride (60% dispersion in mineral oil, 90 mg, 2.2 mmol) in dry THF (1 mL) at 0-5° C. After stirring at 0-5° C. for 5 min., the reaction was stirred at room temperature for 10 min to complete the reaction. The reaction mixture was re-cooled to 0° C. and thiophene-2-sulfonyl chloride (200 mg, 1.1 mmol) dissolved in dry THF (2 mL) was added dropwise. Stirring was continued for 1 h; during this period the reaction mixture slowly attained ambient temperature. THF was removed under reduced pressure. The residue was dissolved in water (10 mL), the pH was adjusted to 10-11 by adding 5N sodium hydroxide solution, and was extracted with ethyl acetate (3×10 mL) to remove the neutral impurities. The aqueous layer was acidified with concentrated HCI (pH 2-3) and extracted with methylene chloride (3×10 mL). The combined organic layers was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give N-(4-bromo-3-methyl-5-isoxazolyl)thiophene-2-sulfonamide. The pure material was obtained by recrystallization using hexanes/ethyl acetate (110 mg, 34% yield), m.p. 125-127° C.

1. stirringthe reaction was stirred at room temperature for 10 min
2. customthe reaction
3. temperatureThe reaction mixture was re-cooled to 0° C.
4. additionwas added dropwise
5. stirringStirring
6. waitwas continued for 1 h
7. waitduring this period the reaction mixture slowly attained ambient temperature
8. customTHF was removed under reduced pressure
9. dissolutionThe residue was dissolved in water (10 mL)
10. additionby adding 5N sodium hydroxide solution
11. extractionwas extracted with ethyl acetate (3×10 mL)
12. customto remove the neutral impurities
13. extractionextracted with methylene chloride (3×10 mL)
14. dry with materialThe combined organic layers was dried over anhydrous magnesium sulfate
15. concentrationconcentrated under reduced pressure

ORD record

ord-4c8095cbeb8442969668b4cda8d066b7

Source dataset

uspto-grants-2001_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06248767B1