Hydrochloric Acid → Ethyl 3-(4-fluoro-2-nitroanilino)-1-methylpyrazole-4-carboxylate

Temperature

-15 °C

A solution of ethyl 3-amino-1-methylpyrazole-4-carboxylate (Helv. Chim. Acta (1959) 42 349) (17 g) in dry tetrahydrofuran (250 ml) was stirred under nitrogen at -10° C. n-Butyl lithium (75 ml of 1.84 molar solution in hexane) was added at -10° to -15° C. The mixture was stirred at -15° C. for 10 minutes and a solution of 2,5-difluoronitrobenzene (16 g) in dry tetrahydrofuran (50 ml) was added at -15° to -10° C. The solution was warmed at room temperature and stirred for 1 hour. The ink-blue solution was poured into 500 ml of a 1:1 mixture of hydrochloric acid (2 M) and ice-brine, extracted with chloroform (3×250 ml), washed with water (2×250 ml), dried with magnesium sulphate and evaporated to dryness. The brick-red residue was crystallised from ethanol (800 ml) to give the title compound having a m.p. of 162° C.

1. additionwas added at -10° to -15° C
2. temperatureThe solution was warmed at room temperature
3. stirringstirred for 1 hour
4. extractionextracted with chloroform (3×250 ml)
5. washwashed with water (2×250 ml)
6. dry with materialdried with magnesium sulphate
7. customevaporated to dryness
8. customThe brick-red residue was crystallised from ethanol (800 ml)

ORD record

ord-c2cf56aede6d4ac6953510bebe4666cd

Source dataset

uspto-grants-1983_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04404137