Sodium hydride → 3-Oxo-2-(3-trifluoromethyl-pyrazol-1-yl)-butyric acid benzyl ester

HRID 1671348Notes

Reaction equation

HRID 1671348 reaction equation
[F:1][C:2]([F:9])([F:8])[C:3]1[CH:7]=[CH:6][NH:5][N:4]=1.[H-].[Na+].[CH2:12]([O:19][C:20](=[O:26])[CH:21](Br)[C:22](=[O:24])[CH3:23])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C1COCC1.O>[CH2:12]([O:19][C:20](=[O:26])[CH:21]([N:5]1[CH:6]=[CH:7][C:3]([C:2]([F:9])([F:8])[F:1])=[N:4]1)[C:22](=[O:24])[CH3:23])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 18070343-(Trifluoromethyl)pyrazoleHCID 10978553Benzyl 2-bromo-3-oxobutanoate

Product 1

HCID 672131393-Oxo-2-(3-trifluoromethyl-pyrazol-1-yl)-butyric acid benzyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 3-trifluoromethylpyrazole (0.703 g, 5.16 mmol) in THF (36.9 ml) is added NaH (0.199 g, 4.98 mmol). The reaction mixture is stirred at RT for 10 mins and then treated with 2-bromo-3-oxo-butyric acid benzyl ester (1.0 g, 3.69 mmol). After stirring at 40° C. for 30 mins, the mixture is diluted with water (50 ml) and extracted with EtOAc (2×50 ml). The combined organics are washed with brine, dried over MgSO4 and concentrated in vacuo. The crude product is purified by ISCO combiflash chromatography, eluting with 0 to 100% (iso-hexane/EtOAc) on a 24 g SiO2-column to afford the title compound; MS: m/z 327.22 [M+H]+

Workup

  1. stirringAfter stirring at 40° C. for 30 mins
  2. extractionextracted with EtOAc (2×50 ml)
  3. washThe combined organics are washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified by ISCO combiflash chromatography
  7. washeluting with 0 to 100% (iso-hexane/EtOAc) on a 24 g SiO2-column

Sources & evidence

ORD record
ord-7eda5b4e4bdf4832a6612aa3dc5a2dcd
Source dataset
uspto-grants-2011_08
Patent number
US07994203B2

Reaction notes

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