Dimethylformamide → HCID 11551131, compound

HRID 2240165Notes

Reaction equation

HRID 2240165 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[CH:14]=[CH:15][C:16]([O:20][CH3:21])=[C:17]([OH:19])[CH:18]=3)=[CH:11][CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:22]N(C)C=O.CI.C(OCC)(=O)C>O>[CH3:22][O:19][C:17]1[CH:18]=[C:13]([C:12]2[N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[N:9]=[CH:10][CH:11]=2)[CH:14]=[CH:15][C:16]=1[O:20][CH3:21]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodide2×HCID 8857Ethyl AcetateHCID 11543755HCID 11543755, compound

Product 1

HCID 11551131HCID 11551131, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

5-[1-(4-Fluorophenyl)-1H-pyrazol-5-yl]-2-methoxyphenol (50.0 mg, 0.176 mmol), 5 mL of N,N-dimethylformamide and methyl iodide (16.4 uL, 0.264 mmol) were combined in a vial and stirred at room temperature overnight. An additional 0.5 mL of methyl iodide was added and stirring continued for 2 days at room temperature and then 10 mL of ethyl acetate and 10 mL of water were added. The organic layer was separated, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a gradient of 10% ethyl acetate in hexanes to 50% ethyl acetate in hexanes over 20 minutes to give 5-(3,4-dimethoxyphenyl)-1-(4-fluorophenyl)-1H-pyrazole (25 mg, 48%) as a white solid. LC/MS (EI) tR 4.14, m/z 299.1 (M++1). 1H NMR (CDCl3 300 MHz) δ 3.7 (s, 3H); 3.9 (s, 3H); 6.5 (s, 1H); 6.7 (s, 1H); 7.0 (s, 2H); 7.1 (m, 2H); 7.3 (m, 2H); 7.7 (s, 1H).

Workup

  1. stirringstirring
  2. waitcontinued for 2 days at room temperature
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel eluting with a gradient of 10% ethyl acetate in hexanes to 50% ethyl acetate in hexanes over 20 minutes

Sources & evidence

ORD record
ord-363e721497474fa89897955630ddc7e0
Source dataset
uspto-grants-2010_05
Patent number
US07723348B2

Reaction notes

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