1-Benzyl-4-piperidone → Methyl 1-(phenylmethyl)-4-piperidineacetate

HRID 501975Notes

Reaction equation

HRID 501975 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([CH2:7]P(OC)(OC)=O)=[O:6].[CH2:14]([N:21]1[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[H][H]>CN(C)C=O.C(OCC)C.[Pt](=O)=O>[CH2:14]([N:21]1[CH2:26][CH2:25][CH:24]([CH2:7][C:5]([O:4][CH3:3])=[O:6])[CH2:23][CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

8

Reactant 4

HCID 192201-Benzyl-4-piperidoneHCID 24758Sodium hydrideHCID 80029Trimethyl phosphonoacetateHCID 178418361HCID 178418361, compound

Product 1

HCID 11011492Methyl 1-(phenylmethyl)-4-piperidineacetateYield 90%

Reagents, catalysts & solvents 3

HCID 345198Adams' catalystCatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (60% in mineral oil, 10.55 g, 264 mmol) was washed with hexanes then suspended in N,N-dimethylformamide (200 mL). Mixture was cooled to 0° C. Trimethyl phosphonoacetate (38.0 mL, 249 mmol) was added to the mixture dropwise. The reaction was stirred at 0° C. for 30 minutes. 1-Benzyl-4-piperidone (40.0 mL, 220 mmol) was added to the reaction mixture dropwise. The reaction was warmed to ambient temperature and held with stirring for 1 h. The reaction mixture was diluted with diethyl ether (500 mL), washed with water (2×), then brine. The organic layer was dried (magnesium sulfate), filtered, and concentrated in vacuo. The residue was dissolved in methanol (220 mL). Platinum(IV) oxide (600 mg, 2.64 mmol) was added to the mixture. The reaction vessel was placed on a Parr apparatus, charged with 40 psi of hydrogen gas, and shaken at room temperature for 5 h. The reaction mixture was removed from the apparatus, filtered through celite, and concentrated. The residue was passed through a short column of silica gel eluting with ethyl acetate. Fractions were concentrated in vacuo. The title compound was obtained as amber oil in 90% yield. 1H NMR (300 MHz, CDCl3): δ 7.31-7.16 (m, 5H), 3.62 (s, 3H), 3.45 (s, 2H), 2.83 (d, J=11.71, 2H), 2.20 (d, J-6.95, 2H), 2.00-1.88 (m, 1H), 1.82-1.69 (m, 1H), 1.69-1.59 (m, 2H), 1.38-1.25 (m, 2H). Mass spec.: 249.3 (MH)+.

Workup

  1. temperatureThe reaction was warmed to ambient temperature
  2. stirringwith stirring for 1 h
  3. washwashed with water (2×)
  4. dry with materialThe organic layer was dried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in methanol (220 mL)
  8. stirringshaken at room temperature for 5 h
  9. customThe reaction mixture was removed from the apparatus
  10. filtrationfiltered through celite
  11. concentrationconcentrated
  12. concentrationFractions were concentrated in vacuo

Sources & evidence

ORD record
ord-d2f3daf102e049f8841f3a5a209082d8
Source dataset
uspto-grants-2010_08
Patent number
US07772244B2

Reaction notes

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