Methyl iodide → 1-(4-Methoxybenzyl)-3-methyl-3-(3,4,5-trifluorophenoxy)piperidin-2-one

HRID 71207Notes

Reaction equation

HRID 71207 reaction equation
[CH3:1][O:2][C:3]1[CH:26]=[CH:25][C:6]([CH2:7][N:8]2[CH2:13][CH2:12][CH2:11][CH:10]([O:14][C:15]3[CH:20]=[C:19]([F:21])[C:18]([F:22])=[C:17]([F:23])[CH:16]=3)[C:9]2=[O:24])=[CH:5][CH:4]=1.[CH3:27][Si](C)(C)[N-][Si](C)(C)C.[Li+].CI>C1COCC1.[Cl-].[NH4+]>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[CH2:13][CH2:12][CH2:11][C:10]([CH3:27])([O:14][C:15]3[CH:16]=[C:17]([F:23])[C:18]([F:22])=[C:19]([F:21])[CH:20]=3)[C:9]2=[O:24])=[CH:25][CH:26]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 666081331-(4-Methoxybenzyl)-3-(3,4,5-trifluorophenoxy)piperidin-2-one

Product 1

HCID 666083191-(4-Methoxybenzyl)-3-methyl-3-(3,4,5-trifluorophenoxy)piperidin-2-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

To a mixture of 1-(4-methoxybenzyl)-3-(3,4,5-trifluorophenoxy)piperidin-2-one (250 mg) in THF (5 mL) was added lithiumhexamethyl disilazide (1M THF solution, 0.821 mL) at −78° C. under a nitrogen atmosphere, and the mixture was stirred for 30 min. To the reaction mixture was added a mixture of methyl iodide in THF (1 mL), and the mixture was stirred at −78° C. for 30 min under a nitrogen atmosphere, and at room temperature for 2 hr. The reaction mixture was diluted with saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The organic layer was separated, washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (89 mg).

Workup

  1. additionTo the reaction mixture was added
  2. stirringthe mixture was stirred at −78° C. for 30 min under a nitrogen atmosphere
  3. waitat room temperature for 2 hr
  4. extractionthe mixture was extracted with ethyl acetate
  5. customThe organic layer was separated
  6. washwashed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-102396721ae44ed6956db27e29b0235d
Source dataset
uspto-grants-2014_09
Patent number
US08822699B2

Reaction notes

Loading…