Methyl iodide → ethyl 1-(3-fluorophenyl)-5-(N-methylacetamido)-1H-pyrazole-4-carboxylate

HRID 659706Notes

Reaction equation

HRID 659706 reaction equation
[C:1]([NH:4][C:5]1[N:9]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=2)[N:8]=[CH:7][C:6]=1[C:17]([O:19][CH2:20][CH3:21])=[O:18])(=[O:3])[CH3:2].[H-].[Na+].[CH3:24]I.[Cl-].[NH4+]>CN(C=O)C.C1COCC1>[F:16][C:12]1[CH:11]=[C:10]([N:9]2[C:5]([N:4]([CH3:24])[C:1](=[O:3])[CH3:2])=[C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:7]=[N:8]2)[CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 57708075ethyl 5-acetamido-1-(3-fluorophenyl)-1H-pyrazole-4-carboxylate

Product 1

HCID 57708074ethyl 1-(3-fluorophenyl)-5-(N-methylacetamido)-1H-pyrazole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of ethyl 5-acetamido-1-(3-fluorophenyl)-1H-pyrazole-4-carboxylate (3.56 g, 12.2 mmol) in 8 mL of DMF and 8 mL of THF at 0° C. was treated with NaH (60% wt. in mineral oil, 850 mg, 21.2 mmol). After 10 min of stirring, MeI (1.4 mL, 21.9 mmol) was added, and the reaction mixture was stirred at 0° C. for 15 min followed by RT for 1 h. the mixture was treated with saturated ammonium chloride and extracted with EtOAc twice. The combined EtOAc layers were washed with brine, dried and concentrated. Purification of the resulting crude material on an ISCO (80 g column, 30-50% EtOAc in Hexanes) provided ethyl 1-(3-fluorophenyl)-5-(N-methylacetamido)-1H-pyrazole-4-carboxylate as a colorless amorphous solid. MS (ESI, pos.ion) m/z: 306.1 (M+1).

Workup

  1. stirringthe reaction mixture was stirred at 0° C. for 15 min
  2. waitfollowed by RT for 1 h.
  3. extractionextracted with EtOAc twice
  4. washThe combined EtOAc layers were washed with brine
  5. customdried
  6. concentrationconcentrated
  7. customPurification of the resulting crude material on an ISCO (80 g column, 30-50% EtOAc in Hexanes)

Sources & evidence

ORD record
ord-6486a3bc76f74066b8f9dee78148bf74
Source dataset
uspto-grants-2011_12
Patent number
US08080546B2

Reaction notes

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