Sodium hydride → Benzyl 4-(3-fluorobenzylidene)piperidine-1-carboxylate

HRID 928048Notes

Reaction equation

HRID 928048 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([CH:16]=[CH:17][CH:18]=1)[CH2:7]P(=O)(OCC)OCC.O=[C:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:27])[CH2:22][CH2:21]1>C1COCC1>[F:3][C:4]1[CH:5]=[C:6]([CH:16]=[CH:17][CH:18]=1)[CH:7]=[C:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[O:27])[CH2:22][CH2:21]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 643496Benzyl 4-oxopiperidine-1-carboxylateHCID 11311157Diethyl 3-fluorobenzylphosphonate2×

Product 1

HCID 70984044Benzyl 4-(3-fluorobenzylidene)piperidine-1-carboxylateYield 79.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (0.245 g) was added portionwise to a solution of diethyl (3-fluorobenzyl)phosphonate (Intermediate 182, 1 g) in THF (40 mL) at 0° C. The mixture was stirred for 30 minutes then benzyl 4-oxopiperidine-1-carboxylate (0.947 g) was added at 0° C. The mixture was allowed to warm to room temperature and stirred for 21.5 hours. The mixture was partitioned between water and ethyl acetate and the organic layer was washed with brine, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-25% to give benzyl 4-(3-fluorobenzylidene)piperidine-1-carboxylate (1.05 g)

Workup

  1. stirringstirred for 21.5 hours
  2. customThe mixture was partitioned between water and ethyl acetate
  3. washthe organic layer was washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customThe filtrate was evaporated to dryness
  7. customthe residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-25%

Sources & evidence

ORD record
ord-009993dd58564eb6a2ffef01eff6c703
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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