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

HRID 2381290Notes

Reaction equation

Cl.NO.[OH-].[K+].[CH3:6][O:7][C:8]([C:10]1[N:11]([CH3:22])[N:12]=[C:13]([N:15]2C(C)=CC=C2C)[CH:14]=1)=[O:9]>C(O)C.O>[CH3:6][O:7][C:8]([C:10]1[N:11]([CH3:22])[N:12]=[C:13]([NH2:15])[CH:14]=1)=[O:9]

Participants

Conditions

Temperature: 105 °C

Procedure

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.

Workup

customThe resulting reaction mixture
temperatureAfter this time, the reaction was cooled to 25° C.
concentrationconcentrated in vacuo
customThe residue was then partitioned between water (150 mL) and diethyl ether (3×75 mL)
washThe combined organics were washed with a saturated aqueous sodium bicarbonate solution (2×150 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-e9c0ae1beb704c8b970c7306e722b590
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08258134B2

Reaction notes

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