Sodium hydride → Tert-butyl 4-(1-ethoxy-1-oxopropan-2-ylidene)piperidine-1-carboxylate

HRID 1804838Notes

Reaction equation

HRID 1804838 reaction equation
[H-].[Na+].C(OP([CH:11]([CH3:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])(OCC)=O)C.O=[C:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1>C1COCC1>[CH2:15]([O:14][C:12](=[O:13])[C:11](=[C:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1)[CH3:17])[CH3:16]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 107155Triethyl 2-phosphonopropionateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 59464295Tert-butyl 4-(1-ethoxy-1-oxopropan-2-ylidene)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 100-mL 3-neck round-bottom flask was charged with anhydrous THF (20 mL) and 60% dispersion sodium hydride (0.574 g, 14.35 mmol) and placed under nitrogen atmosphere. At ambient temperature, ethyl 2-(diethoxyphosphoryl)propanoate (3.42 g, 14.35 mmol) was added to the suspension via syringe over a period of 5 min and the mixture stirred for 30 min. The resulting clear mixture was treated with a solution of tert-butyl 4-oxopiperidine-1-carboxylate (2.2 g, 11.04 mmol) in anhydrous THF (5 mL) and the reaction continued at ambient temperature for 1 h. At the conclusion of this period, the mixture was quenched with saturated NH4Cl solution and the mixture was then extracted with EtOAc (3×50 mL). The extract was washed with brine, dried (MgSO4) and concentrated to give the crude product. The crude product was purified by flash chromatography using an 80 g silica gel gradient elution from 20:1 Hex/EtOAc to 6:1 Hex/EtOAc. The fractions containing the product were pooled and concentrated on a rotary evaporator to give tert-butyl 4-(1-ethoxy-1-oxopropan-2-ylidene)piperidine-1-carboxylate as a colorless liquid. 1H-NMR (500 MHz, CDCl3) δ ppm 4.18 (2 H, q, J=7.15 Hz), 3.43 (4 H, dt, J=23.71, 5.88 Hz), 2.61 (2 H, t, J=5.77 Hz), 2.33 (2 H, t, J=5.77 Hz), 1.86 (3 H, s), 1.45 (9H, s), 1.26-1.31 (3H, m, J=7.15 Hz).

Workup

  1. waitthe reaction continued at ambient temperature for 1 h
  2. customAt the conclusion of this period, the mixture was quenched with saturated NH4Cl solution
  3. extractionthe mixture was then extracted with EtOAc (3×50 mL)
  4. washThe extract was washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customto give the crude product
  8. customThe crude product was purified by flash chromatography
  9. washan 80 g silica gel gradient elution from 20:1 Hex/EtOAc to 6:1 Hex/EtOAc
  10. additionThe fractions containing the product
  11. concentrationconcentrated on a rotary evaporator

Sources & evidence

ORD record
ord-3a8eafc5c8de46368d9369422d3788ad
Source dataset
uspto-grants-2013_01
Patent number
US08354432B2

Reaction notes

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