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 5 N sodium hydroxide solution, and was extracted with ethyl acetate (3×10 ml) to remove the neutral impurities. The aqueous layer was acidified with concentrated HCl (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 5 N 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-647d9eb4b6e44d88b91c7b04e149c7a0

Source dataset

uspto-grants-1999_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05962490