Dimethyl Sulfoxide → 1-Boc-4-Methylenepiperidine

HRID 1241462Notes

Reaction equation

HRID 1241462 reaction equation
[H-].[Na+].[CH3:3]S(C)=O.O=[C:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.O>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1.C(OCC)(=O)C>[CH2:3]=[C:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1

Participants

8

Reactant 4

HCID 679Dimethyl SulfoxideHCID 962WaterHCID 24758Sodium hydrideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 27568081-Boc-4-MethylenepiperidineYield 55%

Reagents, catalysts & solvents 3

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Methyltriphenylphosphonium bromide (9.5 g, 26.7 mmol) was dissolved in THF (33 mL). Sodium hydride (0.675 g, 26.7 mmol) was added portionwise followed by DMSO (33 mL). After stirring for 10 minutes, a solution of tert-butyl 4-oxopiperidine-1-carboxylate (5.0 g, 25 mmol) in THF (25 mL) was added dropwise. The resulting suspension was stirred at room temp for 30 minutes. Water and ethyl acetate were added and the organic phase was washed with aqueous NaHCO3 and brine and was dried (Na2SO4), filtered, and concentrated. The colorless oil was triturated with diethyl ether and the resulting solids were removed by filtration. Concentration of the solvent gave an oil that was purified by flash chromatography eluting with 30%–50% diethyl ether/hexane to provide the desired product as a colorless oil (2.69 g, 55% yield). 1H NMR (300 MHz, CDCl3) δ: 4.70 (2H, s), 3.38 (4H, t, J=5.7 Hz), 2.14 (4H, t, J=5.8 Hz), 1.43 (9H, s).

Workup

  1. stirringThe resulting suspension was stirred at room temp for 30 minutes
  2. washthe organic phase was washed with aqueous NaHCO3 and brine
  3. dry with materialwas dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe colorless oil was triturated with diethyl ether
  7. customthe resulting solids were removed by filtration
  8. customConcentration of the solvent gave an oil that
  9. customwas purified by flash chromatography
  10. washeluting with 30%–50% diethyl ether/hexane

Sources & evidence

ORD record
ord-40d32347af6747f297fc919f643f460d
Source dataset
uspto-grants-2006_10
Patent number
US07115601B2

Reaction notes

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