Potassium Hydroxide → methyl 3-amino-1-methyl-1H-pyrazole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of hydroxylamine hydrochloride (453 mg, 6.52 mmol) in ethanol (4.85 mL) was treated with a solution of potassium hydroxide (197.5 mg, 3.52 mmol) in water (2.93 mL) and ethanol (2.93 mL) followed by addition of 5-(2,5-dimethyl-pyrrol-1-yl)-2-methyl-2H-pyrazole-3-carboxylic acid methyl ester (0.32 g, 1.40 mmol). The resulting reaction mixture was heated in a sealed tube at 105° C. for 3 d. After this time, the reaction was cooled to 25° C. and then concentrated in vacuo. The residue was then partitioned between water (150 mL) and diethyl ether (3×75 mL). The combined organics were washed with a saturated aqueous sodium bicarbonate solution (2×150 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 40 g, 10-100% ethyl acetate/hexanes) afforded 5-amino-2-methyl-2H-pyrazole-3-carboxylic acid methyl ester (34.9 mg, 16%) as an orange-brown solid; ES+-HRMS m/e calcd for C6H9N3O2 [M+H+] 156.0768, found 156.0767.

Provenance & Evidence