Water → Ethyl 3-difluoromethyl-1-methyl-4-pyrazole carboxylate

HRID 1811369Notes

Reaction equation

HRID 1811369 reaction equation
C(O[CH:4]=[C:5]([C:11](=O)[CH:12]([F:14])[F:13])[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.CC1C=CC(S(O)(=O)=O)=CC=1.O.[NH:28]1[CH:32]=CC=[N:29]1>C1(C)C=CC=CC=1>[F:13][CH:12]([F:14])[C:11]1[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][N:28]([CH3:32])[N:29]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1048PyrazoleHCID 6101p-Toluenesulfonic acidHCID 53395411Butanoic acid, 2-(ethoxymethylene)-4,4-difluoro-3-oxo-, ethyl ester

Product 1

HCID 11644126Ethyl 3-difluoromethyl-1-methyl-4-pyrazole carboxylateYield 73%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

The aminal (1.00 g, 2.81 mmol) was dissolved in 7 mL of toluene. Then, ethyl α-ethoxymethylene-4,4-difluoro-3-oxobutyrate (1.25 g, 5.62 mmol) and p-TsOH (107 mg, 0.56 mmol) were added, followed by water (101 mg, 5.62 mg). The mixture was stirred at rt for 90 min, then GC control showed >97% conversion to the pyrazole. The reaction mixture was extracted with water (2×1 mL); then, the organic phase was concentrated under reduced pressure and the residue purified by column chromatography (SiO2, cyclohexane/EtOAc 100:0→70:30) to give the product (840 mg, 4.12 mmol, 73% yield) as a colorless solid.

Workup

  1. extractionThe reaction mixture was extracted with water (2×1 mL)
  2. concentrationthen, the organic phase was concentrated under reduced pressure
  3. customthe residue purified by column chromatography (SiO2, cyclohexane/EtOAc 100:0→70:30)

Sources & evidence

ORD record
ord-b477574a055948ef9133a4f595ecbb88
Source dataset
uspto-grants-2013_01
Patent number
US08362272B2

Reaction notes

Loading…