Methanol → Methyl 1-(difluoromethyl)-1H-pyrazole-3-carboxylate

HRID 593371Notes

Reaction equation

HRID 593371 reaction equation
[F:1][CH:2]([F:11])[N:3]1[CH:7]=[CH:6][C:5]([C:8]([OH:10])=[O:9])=[N:4]1.S(=O)(=O)(O)O.[CH3:17]O>>[CH3:17][O:9][C:8]([C:5]1[CH:6]=[CH:7][N:3]([CH:2]([F:1])[F:11])[N:4]=1)=[O:10]

Participants

4

Procedure

A solution of 1-difluoromethyl-1H-pyrazole-3-carboxylic acid (CAS925179-02-8) (500 mg, 3.1 mmol) in methanol (18 ml) was cooled to 0° C. and treated with sulphuric acid (98%, 0.2 ml, 3.1 mmol). The mixture was heated to reflux for 2 hours. For the workup, the solution was cooled and concentrated at reduced pressure. The residue was partitioned between ethyl acetate (25 ml) and water (30 ml). The organic layer was separated, washed with water until the water phase showed a neutral pH. After drying over sodium sulphate, the organic layer was evaporated at reduced pressure. The 1-difluoromethyl-1H-pyrazole-3-carboxylic acid methyl ester was obtained as a colorless liquid (535 mg, 99%) pure enough to be engaged in the next step without further purification; (calculated) C6H6F2N2O2 [176.12]; (found) [M+H]+=177.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 2 hours
  3. temperatureFor the workup, the solution was cooled
  4. concentrationconcentrated at reduced pressure
  5. customThe residue was partitioned between ethyl acetate (25 ml) and water (30 ml)
  6. customThe organic layer was separated
  7. washwashed with water until the water phase
  8. dry with materialAfter drying over sodium sulphate
  9. customthe organic layer was evaporated at reduced pressure

Sources & evidence

ORD record
ord-434a0705c7894e0f989f5e23ff0e5fa6
Source dataset
uspto-grants-2016_01
Patent number
US09242943B2

Reaction notes

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