Dimethyl Sulfate → Methyl 4-[2-fluoro-4-(trifluoromethyl)phenyl]-1,2-dimethyl-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxylate

HRID 734708Notes

Reaction equation

HRID 734708 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[CH:12]1[CH2:17][C:16](=[O:18])[NH:15][C:14]([CH3:19])=[C:13]1[C:20]([O:22][CH3:23])=[O:21].[H-].[Na+].[CH3:26]OS(OC)(=O)=O>CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:9])([F:11])[F:10])[CH:5]=[CH:4][C:3]=1[CH:12]1[CH2:17][C:16](=[O:18])[N:15]([CH3:26])[C:14]([CH3:19])=[C:13]1[C:20]([O:22][CH3:23])=[O:21]

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 24758Sodium hydrideHCID 68826908Methyl 4-[2-fluoro-4-(trifluoromethyl)phenyl]-2-methyl-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxylate

Product 1

HCID 68827826Methyl 4-[2-fluoro-4-(trifluoromethyl)phenyl]-1,2-dimethyl-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxylateYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The product of Example 21, Step 1 (3.0 g, 9.056 mmol, 1.0 equiv) was dissolved in 100 mL DMF and NaH (725 mg, 18.11 mmol, 2.0 equiv) was added slowly to the reaction mixture. Me2SO4 (1.72 mL, 18.11 mmol, 2.0 equiv) was added and the reaction was stirred at room temperature for 45 min. The reaction was quenched with water and diluted with EtOAc. After the phases were separated, the organic phase was washed once with satd. NaHCO3 and once with satd. NaCl. The organic phase was dried over Na2SO4, filtered, and concentrated en vacuo. The residue was triturated with Et2O and filtered to provide 1.5 g (48%) of the title compound as a light yellow solid. MS (ES+) m/e 346 [M+H]+

Workup

  1. customThe reaction was quenched with water
  2. additiondiluted with EtOAc
  3. customAfter the phases were separated
  4. washthe organic phase was washed once with satd
  5. dry with materialThe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated en vacuo
  8. customThe residue was triturated with Et2O
  9. filtrationfiltered

Sources & evidence

ORD record
ord-72d5cb15a1334670b1e653e8d07618be
Source dataset
uspto-grants-2009_09
Patent number
US07592357B2

Reaction notes

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