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

HRID 278220Notes

Reaction equation

HRID 278220 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+].[CH2:20]([O:27][C:28]([N:30]1[CH2:35][CH2:34][CH:33]([CH:36]=O)[CH2:32][CH2:31]1)=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C1COCC1>[CH2:20]([O:27][C:28]([N:30]1[CH2:35][CH2:34][CH:33]([CH:36]=[CH:3][C:2](=[O:1])[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:32][CH2:31]1)=[O:29])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 372803Diethyl 2-oxo-2-phenylethylphosphonateHCID 2776272Benzyl 4-formylpiperidine-1-carboxylate

Product 1

HCID 570744891-(Benzyloxycarbonyl)-4-(3-oxo-3-phenylprop-1-enyl)piperidineYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Diethyl (2-oxo-2-phenylethyl)phosphonate (0.96 mL, 1.1 g, 4.4 mmol) was added in one portion to a stirred suspension of sodium hydride (60% oil dispersion, 158 mg, 3.95 mmol) in THF (20 mL). After 15 min. at rt, the clear solution was cooled in an ice bath and 1-(benzyloxycarbonyl)-4-piperidinecarboxaldehyde (840 mg, 3.40 mmol) was added in THF (1.0 mL) with additional THF (2×1.0 mL) for rinsing. Stirring was continued for a total of 2 h, with slow warming to rt. The mixture was then partitioned between ether (120 mL) and 2.5 N aq. NaOH (60 mL). The organic layer was washed with saturated aq. brine (60 mL), dried (sodium sulfate), decanted, and evaporated. The crude product was purified by FC, eluting with 15-20% ethyl acetate in hexane, to give 0.95 g of the title compound as a colorless syrup.

Workup

  1. temperaturethe clear solution was cooled in an ice bath
  2. washfor rinsing
  3. customwas continued for a total of 2 h
  4. customThe mixture was then partitioned between ether (120 mL) and 2.5 N aq. NaOH (60 mL)
  5. washThe organic layer was washed with saturated aq. brine (60 mL)
  6. dry with materialdried (sodium sulfate)
  7. customdecanted
  8. customevaporated
  9. customThe crude product was purified by FC
  10. washeluting with 15-20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-d8f24cbc4070496f867a1929c49be4c8
Source dataset
uspto-grants-2002_03
Patent number
US06358979B1

Reaction notes

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