Sodium hydride → Tert-butyl 4-(2-methoxy-2-oxoethylidene)piperidine-1-carboxylate

HRID 2378621Notes

Reaction equation

HRID 2378621 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([CH2:7]P(OC)(OC)=O)=[O:6].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]>CN(C)C=O.C(OCC)C>[CH3:3][O:4][C:5](=[O:6])[CH:7]=[C:24]1[CH2:25][CH2:26][N:21]([C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:20])[CH2:22][CH2:23]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 80029Trimethyl phosphonoacetateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 10377658Tert-butyl 4-(2-methoxy-2-oxoethylidene)piperidine-1-carboxylateYield 92%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

60% sodium hydride in mineral oil (7.92 g, 198.02 mmoles) was washed with hexanes then suspended in N,N-dimethylformamide (220.00 mL). The mixture was cooled to 0° C. Trimethyl phosphonoacetate (29.0 mL,189.82 mmoles) was added drop-wise to the reaction. The mixture was held at 0° C. with stirring on and held for 20 min. A solution of N-tert-butoxycarbonyl-4-piperidone (30.41 g, 152.62 mmoles) in 80 mL N,N-dimethylformamide was added to the mixture drop-wise. Reaction was stirred at room temperature for 3 hours. Mixture was diluted with diethyl ether (650 mL). Mixture was washed once with water. Aqueous layer was back extracted once with diethyl ether. Organic layers were combined. The mixture was washed 4 times with water and the aqueous phase was discarded. The mixture was washed with brine and the aqueous phase was discarded. The material was dried over MgSO4, filtered, and concentrated to dryness. Title compound was obtained as white solid in 92% yield. 1H NMR (300 MHz, CDCl3): δ=5.68 (s, 1H), 3.66 (s, 3H), 3.40-3.51 (m, 4H), 2.90 (t, J=5.49, 2H), 2.25 (t, J=5.49, 2H), 1.44 (s, 9H).

Workup

  1. customto the reaction
  2. customwas held at 0° C.
  3. customReaction
  4. stirringwas stirred at room temperature for 3 hours
  5. washMixture was washed once with water
  6. extractionAqueous layer was back extracted once with diethyl ether
  7. washThe mixture was washed 4 times with water
  8. washThe mixture was washed with brine
  9. dry with materialThe material was dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-b48f9c815d4a4d99904a66cf1d0bd462
Source dataset
uspto-grants-2008_12
Patent number
US07470679B2

Reaction notes

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