Sodium hydride → HCID 68509507, compound

HRID 1257318Notes

Reaction equation

HRID 1257318 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][NH:5][N:4]=1.[H-].[Na+].Br[CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20]>CN(C)C=O.O>[CH2:11]([O:10][C:8]([C:7]1[C:3]([C:2]([F:1])([F:13])[F:14])=[N:4][N:5]([CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH:6]=1)=[O:9])[CH3:12]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 178469923HCID 178469923, compound

Product 1

HCID 68509507HCID 68509507, compoundYield 75.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of ethyl 3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (6.24 g, 30.0 mmol) in N,N-dimethylformamide (60 ml) was added under ice-cooling 60% sodium hydride (1.80 g, 45.0 mmol) by a small amount and the mixture was stirred for 30 min. tert-Butyl bromoacetate (5.32 mL, 36.0 mmol) was added to the reaction mixture under ice-cooling, and the mixture was stirred at room temperature for 4 hr. The reaction mixture was diluted with water, extracted with ethyl acetate, washed successively with water and saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (carrier: silica gel, eluent: hexane-ethyl acetate) to give tert-butyl [4-(ethoxycarbonyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetate (7.33 g, 75%) as a colorless oil. Trifluoroacetic acid (30 mL) was added to the present compound (3.22 g, 10.0 mmol), and the mixture was stirred under ice-cooling for 2.5 hr. The reaction mixture was concentrated under reduced pressure, and the residue was recrystallized from ethyl acetate-hexane to give the title compound (2.03 g, 76%) as colorless crystals.

Workup

  1. additionwas added to the reaction mixture under ice-
  2. temperaturecooling
  3. extractionextracted with ethyl acetate
  4. washwashed successively with water and saturated brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography (carrier: silica gel, eluent: hexane-ethyl acetate)

Sources & evidence

ORD record
ord-9c710e67693d48fe939f8e5d3e52adb2
Source dataset
uspto-grants-2013_06
Patent number
US08461348B2

Reaction notes

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