Methanol → Methyl 1-(difluoromethyl)-1H-pyrazole-3-carboxylate
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
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% of theory) pure enough to be engaged in the next step without further purification. MS (ISP): m/z=177.1 [M+H]+.
Workup
- temperatureThe mixture was heated
- temperatureto reflux for 2 hours
- temperatureFor the workup, the solution was cooled
- concentrationconcentrated at reduced pressure
- customThe residue was partitioned between ethyl acetate (25 ml) and water (30 ml)
- customThe organic layer was separated
- washwashed with water until the water phase
- dry with materialAfter drying over sodium sulphate
- customthe organic layer was evaporated at reduced pressure
Sources & evidence
- ORD record
- ord-e50b91b346ae48a09d49fdfc15ee7e9c
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08754075B2
Reaction notes
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