Methyl iodide → ethyl 5-(2-fluoro-4-(2-methoxy-4,6-dimethylpyridin-3-yl)phenyl)-1-[(3RS,4SR)-4-methoxytetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate

HRID 1043968Notes

Reaction equation

HRID 1043968 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[C:8]([C:10]2[C:11]([O:18][CH3:19])=[N:12][C:13]([CH3:17])=[CH:14][C:15]=2[CH3:16])[CH:7]=[CH:6][C:5]=1[C:20]1[N:24]([CH:25]2[CH:29]([OH:30])[CH2:28][O:27][CH2:26]2)[N:23]=[CH:22][C:21]=1[C:31]([O:33][CH2:34][CH3:35])=[O:32].[CH3:36]I.[Cl-].[NH4+]>C1COCC1>[F:3][C:4]1[CH:9]=[C:8]([C:10]2[C:11]([O:18][CH3:19])=[N:12][C:13]([CH3:17])=[CH:14][C:15]=2[CH3:16])[CH:7]=[CH:6][C:5]=1[C:20]1[N:24]([CH:25]2[CH:29]([O:30][CH3:36])[CH2:28][O:27][CH2:26]2)[N:23]=[CH:22][C:21]=1[C:31]([O:33][CH2:34][CH3:35])=[O:32]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 86686402ethyl 5-(2-fluoro-4-(2-methoxy-4,6-dimethylpyridin-3-yl)phenyl)-1-[(3RS,4SR)-4-hydroxytetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate

Product 1

HCID 86686404ethyl 5-(2-fluoro-4-(2-methoxy-4,6-dimethylpyridin-3-yl)phenyl)-1-[(3RS,4SR)-4-methoxytetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% oil dispersion, 86 mg) was added to a solution of ethyl 5-(2-fluoro-4-(2-methoxy-4,6-dimethylpyridin-3-yl)phenyl)-1-[(3RS,4SR)-4-hydroxytetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate (612 mg) in THF (5 mL) under ice-cooling, followed by stirring for three minutes. Methyl iodide (0.142 mL) was added to the reaction mixture, and the mixture was stirred at the same temperature for five minutes, and then warmed to room temperature and stirred for further two hours. A saturated aqueous ammonium chloride solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated, and the residue was purified by silica gel column chromatography (ethyl acetate/n-heptane, 27% to 48%) to give the title compound (379 mg).

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at the same temperature for five minutes
  3. stirringstirred for further two hours
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated
  9. customthe residue was purified by silica gel column chromatography (ethyl acetate/n-heptane, 27% to 48%)

Sources & evidence

ORD record
ord-94e1b45400a44d0ea37ff9ee46b18164
Source dataset
uspto-grants-2013_10
Patent number
US08563565B2

Reaction notes

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