Methylhydrazine → 3-cyclopropyl-1-methyl-1H-pyrazole-4-carboxylic acid

A mixture of methyl 3-cyclopropyl-3-oxopropanoate (10.0 g, 70.4 mmol) and 1,1-dimethoxy-N,N-dimethylmethanamine (10.1 g, 84.4 mmol) was stirred for 1 hr. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in diethyl ether (25 mL). A solution of methylhydrazine (3.56 g, 77.4 mmol) in diethyl ether (25 mL) was added dropwise with stirring under ice-cooling, and the mixture was stirred for 1 hr. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, ethanol (35 mL) and 8N aqueous sodium hydroxide solution (17.5 mL) were added to the residue, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was neutralized with 1N hydrochloric acid, and the precipitated solid was collected by filtration and washed with water to give a mixture (8.71 g, 75%) of 3-cyclopropyl-1-methyl-1H-pyrazole-4-carboxylic acid (1) and 5-cyclopropyl-1-methyl-1H-pyrazole-4-carboxylic acid (2) as a white solid.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. dissolutionthe residue was dissolved in diethyl ether (25 mL)
3. stirringwith stirring under ice-
4. temperaturecooling
5. stirringthe mixture was stirred for 1 hr
6. washwashed with water and saturated brine
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltrated
9. concentrationThe filtrate was concentrated under reduced pressure, ethanol (35 mL) and 8N aqueous sodium hydroxide solution (17.5 mL)
10. additionwere added to the residue
11. stirringthe mixture was stirred at room temperature for 15 hr
12. filtrationthe precipitated solid was collected by filtration
13. washwashed with water

ORD record

ord-79ee0ce147f84617b9a656ff2d0be6a9

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08304557B2