Hydrochloric Acid → 1-(4-Methoxybenzyl)-3-(3,4,5-trifluorophenoxy)piperidin-2-one

HRID 71206Notes

Reaction equation

HRID 71206 reaction equation
[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][N:8]2[CH2:13][CH2:12][CH2:11][C:10]([O:19][C:20]3[CH:25]=[C:24]([F:26])[C:23]([F:27])=[C:22]([F:28])[CH:21]=3)(C(OCC)=O)[C:9]2=[O:29])=[CH:5][CH:4]=1.[OH-].[Na+].Cl>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[CH2:13][CH2:12][CH2:11][CH:10]([O:19][C:20]3[CH:21]=[C:22]([F:28])[C:23]([F:27])=[C:24]([F:26])[CH:25]=3)[C:9]2=[O:29])=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66607388Ethyl 1-(4-methoxybenzyl)-2-oxo-3-(3,4,5-trifluorophenoxy)piperidine-3-carboxylate

Product 1

HCID 666081331-(4-Methoxybenzyl)-3-(3,4,5-trifluorophenoxy)piperidin-2-oneYield 85.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of ethyl 1-(4-methoxybenzyl)-2-oxo-3-(3,4,5-trifluorophenoxy)piperidine-3-carboxylate (352 mg) and 1N aqueous sodium hydroxide solution (1.6 mL) in THF (3 mL) was stirred at room temperature for 2 days, and acidified with 1N hydrochloric acid, and 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 recrystallized from ethyl acetate/hexane, the white crystals were separated by filtration, and the filtrate was concentrated. A mixture of the residue and the white crystals in toluene (3 mL) was stirred at 100° C. for 1 hr, and the solvent was evaporated under reduced pressure to give the title compound (252 mg).

Workup

  1. extractionextracted with ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was recrystallized from ethyl acetate/hexane
  7. customthe white crystals were separated by filtration
  8. concentrationthe filtrate was concentrated
  9. additionA mixture of the residue
  10. stirringthe white crystals in toluene (3 mL) was stirred at 100° C. for 1 hr
  11. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-2ca7903418af4c3a859603f1cb70c681
Source dataset
uspto-grants-2014_09
Patent number
US08822699B2

Reaction notes

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