Sodium hydride → N-t-butoxycarbonyl-4-(4-fluorobenzylidene)piperidine

HRID 1596301Notes

Reaction equation

HRID 1596301 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][C:11]1=O)=[O:9])([CH3:6])([CH3:5])[CH3:4].[F:17][C:18]1[CH:32]=[CH:31][C:21]([CH2:22]P(=O)(OCC)OCC)=[CH:20][CH:19]=1.C(=O)(O)[O-].[Na+]>O1CCCC1.C1OCCOCCOCCOCCOC1>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C:13](=[CH:22][C:21]2[CH:31]=[CH:32][C:18]([F:17])=[CH:19][CH:20]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 7577838tert-Butyl 2-oxopiperidine-1-carboxylateHCID 11064685Diethyl P-((4-fluorophenyl)methyl)phosphonate

Product 1

HCID 22676694N-t-butoxycarbonyl-4-(4-fluorobenzylidene)piperidineYield 63.2%

Reagents, catalysts & solvents 2

HCID 3633615-Crown-5CatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred suspension of 13.20 g of 60% sodium hydride (in oil) containing 1.65 g of 15-crown-5 ether in 650 ml of tetrahydrofuran were added dropwise a solution of 59.78 g of N-t-butoxycarbonylpiperidone and 81.25 g of diethyl 4-fluorobenzylphosphonate in 150 ml of tetrahydrofuran under ice-cooling over 20 minutes. After stirring at room temperature for a day, a saturated aqueous sodium bicarbonate solution was added cautiously, followed by extracting with ethyl acetate. The extract was washed with a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution, successively, and dried over anhydrous sodium sulfate, followed by removal of the drying agent by filtration. The filtrate was concentrated under reduced pressure and purified by a flash column chromatography (silica gel: Wakogel C200 (manufactured by Wako Pure Chemicals), eluent; hexane-ethyl acetate =20:1) to give 55.23 g of N-t-butoxycarbonyl-4-(4-fluorobenzylidene)piperidine as an oil, which was then crystallized by allowing to stand at room temperature overnight.

Workup

  1. temperaturecooling over 20 minutes
  2. extractionby extracting with ethyl acetate
  3. washThe extract was washed with a saturated aqueous sodium bicarbonate solution
  4. dry with materiala saturated aqueous sodium chloride solution, successively, and dried over anhydrous sodium sulfate
  5. customfollowed by removal of the drying agent by filtration
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. custompurified by a flash column chromatography (silica gel: Wakogel C200 (manufactured by Wako Pure Chemicals), eluent; hexane-ethyl acetate =20:1)

Sources & evidence

ORD record
ord-8ece0efcac314d91a36c3a597ef8a456
Source dataset
uspto-grants-2001_09
Patent number
US06291467B1

Reaction notes

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