Potassium tert-butoxide → Tert-butyl 4-methylene-2-phenylpiperidine-1-carboxylate

HRID 473796Notes

Reaction equation

HRID 473796 reaction equation
[CH3:1]C(C)([O-])C.[K+].O=[C:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:10]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:9]1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1>[CH2:1]=[C:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:10]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:9]1

Participants

5

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 445586011-Boc-2-phenyl-piperidin-4-one

Product 1

HCID 67505825Tert-butyl 4-methylene-2-phenylpiperidine-1-carboxylateYield 96.4%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
40 °C

Procedure

A suspension of potassium tert-butoxide (1.25 g, 11.1 mmol) and methyltriphenylphosphonium bromide (3.86 g, 1.1 mmol) in tetrahydrofuran (100 mL) was stirred at 40° C. for 30 minutes. The mixture was then cooled to room temperature and a solution of tert-butyl 4-oxo-2-phenylpiperidine-1-carboxylate (2.35 g, 8.5 mmol) in tetrahydrofuran (30 mL) was added slowly. The reaction mixture was stirred at 40° C. for 24 hours. The mixture was cooled to room temperature and quenched by the addition of water and diluted with ethyl acetate (250 mL), The organic layer was separated then washed with water, 10% aqueous citric acid and brine, dried over anhydrous sodium sulfate, filtered and concentrated. Column chromatography on silica gel (hexane:ethyl acetate 95:5 to 9:1) provided tert-butyl 4-methylene-2-phenylpiperidine-1-carboxylate (2.24 g, 96%). 1H NMR (400 MHz, CDCl3): 7.31 (m, 4H), 7.21 (m, 1H), 5.48 (br d, 1H), 4.84 (dd, 2H), 4.07 (br dd, 1H), 2.85 (br, t, 1H), 2.78 (dtr, 1H), 2.64 (dd, 1H), 2.28 (dtr, 1H), 2.20 (br d, 1H), 1.42 (s, 9H). GC/MS (EI) for C17H23NO2: 273 (M+).

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. stirringThe reaction mixture was stirred at 40° C. for 24 hours
  3. temperatureThe mixture was cooled to room temperature
  4. customquenched by the addition of water
  5. additiondiluted with ethyl acetate (250 mL)
  6. customThe organic layer was separated
  7. washthen washed with water, 10% aqueous citric acid and brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-5ad4db44006b49de88e8bb1d353ce4b5
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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