p-Toluenesulfonic acid → 1-(3-chloro-4-fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid tert-butyl ester
Reaction equation
[C:1]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])(=[O:6])[CH2:2][C:3]([CH3:5])=O.[CH3:12]OC(OC)N(C)C.CC1C=CC(S(O)(=O)=O)=CC=1.Cl.[Cl:32][C:33]1[CH:34]=[C:35]([NH:40][NH2:41])[CH:36]=[CH:37][C:38]=1[F:39]>CCOC(C)=O>[C:8]([O:7][C:1]([C:2]1[CH:12]=[N:41][N:40]([C:35]2[CH:36]=[CH:37][C:38]([F:39])=[C:33]([Cl:32])[CH:34]=2)[C:3]=1[CH3:5])=[O:6])([CH3:11])([CH3:10])[CH3:9]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 130 °C
Procedure
To a mixture of tert-butyl acetoacetate (1.1 mL, 6.8 mmol) and dimethylformamide-dimethylacetal (1.0 mL, 7.6 mmol) in a microwave tube is added a catalytic amount of TsOH. The yellow solution is heated at 130° C. in the microwave for 15 min. The resultant dark red solution is then cooled to room temperature, concentrated in vacuo and dissolved in acetonitrile (5.0 mL). Triethylamine (2.5 mL) is added followed by 3-chloro-4-fluorophenylhydrazine hydrochloride (1.3 g, 6.8 mmol). The dark reddish brown solution is stirred at room temperature for 16 hours. The reaction is diluted with EtOAc (75 mL) and washed with water (7×50 mL). The combined organic phases are dried over MgSO4, filtered and concentrated in vacuo to afford 1-(3-chloro-4-fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid tert-butyl ester as a dark brown oil (2.1 g, 100%) which is used without further purification.
Workup
- temperatureThe resultant dark red solution is then cooled to room temperature
- concentrationconcentrated in vacuo
- dissolutiondissolved in acetonitrile (5.0 mL)
- additionTriethylamine (2.5 mL) is added
- washwashed with water (7×50 mL)
- dry with materialThe combined organic phases are dried over MgSO4
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-ca343b308c254e53ab22e125180f2db3
- Source dataset
- uspto-grants-2012_10
- Patent number
- US08293917B2
Reaction notes
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