Sodium hydride → 1-(Tert-butoxycarbonyl)-4-(3-oxo-3-phenylprop-1-enyl)piperidine

HRID 2185560Notes

Reaction equation

HRID 2185560 reaction equation
[O:1]=[C:2]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:3]P(=O)(OCC)OCC.[H-].[Na+].[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30]([CH:33]=O)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21]>C1COCC1>[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30]([CH:33]=[CH:3][C:2](=[O:1])[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:21])[CH3:22]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 372803Diethyl 2-oxo-2-phenylethylphosphonateHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylate

Product 1

HCID 572487181-(Tert-butoxycarbonyl)-4-(3-oxo-3-phenylprop-1-enyl)piperidineYield 76.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Diethyl (2-oxo-2-phenylethyl)phosphonate (0.255 mL, 301 mg, 1.17 mmol) was added in one portion to a stirred suspension of sodium hydride (60% oil dispersion, 45 mg, 1.13 mmol) in THF (7 mL) at rt. After 15 min, a portion (1.8 mL) of the clear solution was removed and discarded, and the remainder cooled in an ice bath. 1-(tert-Butoxycarbonyl)-4-piperidinecarboxaldehyde (177 mg, 0.830 mmol, from Step B) was added in THF (1.0 mL) with additional THF (2×1.0 mL) for rinsing. After 16 h at rt, the mixture was then partitioned between ether (40 mL) and 2.5 N aq. NaOH (20 mL). The organic layer was washed with sat'd NaCl (20 mL), dried (Na2SO4), decanted, and evaporated. The crude product was purified by flash column chromatography on silica gel, eluting with 10% EtOAc in hexane, to give 201 mg of 1-(tert-butoxycarbonyl)-4-(3-oxo-3-phenylprop-1-enyl)piperidine as a colorless oil. Hydrogenation of this material using 5% Pd/C in 95% ethanol at atmospheric pressure yielded the title compound as a white crystalline solid.

Workup

  1. customa portion (1.8 mL) of the clear solution was removed
  2. temperaturethe remainder cooled in an ice bath
  3. washfor rinsing
  4. waitAfter 16 h at rt
  5. customthe mixture was then partitioned between ether (40 mL) and 2.5 N aq. NaOH (20 mL)
  6. washThe organic layer was washed with sat'd NaCl (20 mL)
  7. dry with materialdried (Na2SO4)
  8. customdecanted
  9. customevaporated
  10. customThe crude product was purified by flash column chromatography on silica gel
  11. washeluting with 10% EtOAc in hexane

Sources & evidence

ORD record
ord-d4a8e246db58494ba7e76ac4cbd3f243
Source dataset
uspto-grants-2002_06
Patent number
US06399619B1

Reaction notes

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