Sodium hydride → Methyl 4-(3-methyl-pyrazol-1-yl)-2-trifluoromethyl-benzoate

HRID 1978181Notes

Reaction equation

HRID 1978181 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:8]=[CH:7][NH:6][N:5]=1.[CH3:9][O:10][C:11](=[O:24])[C:12]1[CH:17]=[CH:16][C:15](F)=[C:14](C)[C:13]=1[C:20]([F:23])([F:22])[F:21]>CCCCCC.CN(C)C=O>[CH3:9][O:10][C:11](=[O:24])[C:12]1[CH:17]=[CH:16][C:15]([N:6]2[CH:7]=[CH:8][C:4]([CH3:3])=[N:5]2)=[CH:14][C:13]=1[C:20]([F:21])([F:23])[F:22]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 53892546Methyl 4-fluoro-2-trifluoromethylbenzoic acid methyl esterHCID 178428694HCID 178428694, compound

Product 1

HCID 15541085Methyl 4-(3-methyl-pyrazol-1-yl)-2-trifluoromethyl-benzoateYield 59.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8058HexaneSolvent

Procedure

Sodium hydride (60% suspension in oil, 3.85 g, 96.3 mmol) was washed with hexane, dried under nitrogen and resuspended in dry dimethylformamide (150 mL). A solution of 3-methylpyrazole (7.75 mL, 96.3 mmol) in dimethylformamide (50 mL) was added dropwise at ambient temperature. Stirring was continued until the gas evolution subsided, and then a solution of methyl 4-fluoro-2-trifluoromethylbenzoic acid methyl ester of Step A (17.8 g, 80.1 mmol) in dimethylformamide (50 mL) was added dropwise to the clear solution. After stirring for 30 min at room temperature, the reaction was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate. The organic extracts were dried over sodium sulfate and evaporated to dryness. The residue was dissolved in 1:1 mixture of dichloromethane and hexane and absorbed onto a silica Merck-60 flash column. Elution with a dichloromethane-hexane gradient (from 1:1 to 4:1) provided the title compound (13.6 g) as a white solid, m.p. 59-61° C.

Workup

  1. customdried under nitrogen
  2. stirringAfter stirring for 30 min at room temperature
  3. customthe reaction was quenched with saturated aqueous ammonium chloride
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic extracts were dried over sodium sulfate
  6. customevaporated to dryness
  7. dissolutionThe residue was dissolved in 1:1 mixture of dichloromethane and hexane
  8. customabsorbed onto a silica Merck-60 flash column
  9. washElution with a dichloromethane-hexane gradient (from 1:1 to 4:1)

Sources & evidence

ORD record
ord-b47afd7546054f7c933bd9e1e2320e0c
Source dataset
uspto-grants-2001_05
Patent number
US06235900B1

Reaction notes

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