Acetic Anhydride → N-(3-chloro-1H-pyrazol-4-yl)acetamide

Temperatur

5 °C

A 100-mL 3-neck round bottom flask was charged with 3-chloro-1H-pyrazol-4-amine hydrochloride (5.00 g, 32.5 mmol) and water (25 mL). Sodium bicarbonate (10.9 g, 130 mmol) was added slowly over 10 minutes (off-gassing during addition), followed by tetrahydrofuran (25 mL). The mixture was cooled to 5° C. and acetic anhydride (3.48 g, 34.1 mmol) was added over 30 minutes while maintaining the internal temperature at <10° C. The reaction was stirred at 5° C. for 1 hour, at which point thin layer chromatography (TLC) analysis [Eluent: ethyl acetate] indicated that the starting material had disappeared and a major product was exclusively formed. The reaction mixture was diluted with ethyl acetate (25 mL) and water (25 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×25 mL). The combined organic layers were concentrated to afford an off-white solid, which was suspended in methyl tert-butylether (20 mL), stirred for 1 hour, and filtered. The solid was rinsed with methyl tert-butylether (20 mL) and further dried under vacuum at room temperature (about 22° C.) for 4 hours to give a white solid (4.28 g, 83%): mp 162-164° C.; 1H NMR (400 MHz, DMSO-d6) δ 12.90 (bs, 1H), 9.49 (s, 1H), 7.97 (s, 1H), 2.02 (s, 3H); 13C NMR (101 MHz, DMSO-d6) δ 167.81, 130.07, 123.72, 116.73, 22.58; EIMS m/z 159 ([M]+).

1. addition(off-gassing during addition)
2. temperaturewhile maintaining the internal temperature at <10° C
3. customa major product was exclusively formed
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with ethyl acetate (3×25 mL)
6. concentrationThe combined organic layers were concentrated
7. customto afford an off-white solid, which
8. filtrationfiltered
9. washThe solid was rinsed with methyl tert-butylether (20 mL)
10. customfurther dried under vacuum at room temperature (about 22° C.) for 4 hours

ORD-Eintrag

ord-be3ed003d842471ea3a4ae95facf34f8

Quelldatensatz

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09029554B1