Tert-butyl 3-oxopiperidine-1-carboxylate → Tert-butyl 3-[1-(3-fluorophenyl)methylidene]piperidine-1-carboxylate

HRID 928080Notes

Reaction equation

HRID 928080 reaction equation
[Br-].[F:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][CH:28]=1)[CH2:6][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+].O=[C:36]1[CH2:41][CH2:40][CH2:39][N:38]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:37]1>C1COCC1.O>[F:2][C:3]1[CH:4]=[C:5]([CH:6]=[C:40]2[CH2:41][CH2:36][CH2:37][N:38]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:39]2)[CH:26]=[CH:27][CH:28]=1

Participants

6

Reactant 3

HCID 2756825Tert-butyl 3-oxopiperidine-1-carboxylateHCID 10527583Phosphonium, [(3-fluorophenyl)methyl]triphenyl-, bromide2×HCID 23676156Sodium t-butoxide

Product 1

HCID 86713375Tert-butyl 3-[1-(3-fluorophenyl)methylidene]piperidine-1-carboxylateYield 48.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

(3-Fluorobenzyltriphenylphosphonium bromide (Intermediate 228, 5.3 g) was added in portions to a solution of sodium tert-butoxide (1.06 g) in anhydrous THF (20 mL) at room temperature and the mixture was stirred for 30 minutes. A solution of tert-butyl 3-oxopiperidine-1-carboxylate (2 g) in anhydrous THF (10 mL) was added dropwise at room temperature and the mixture was stirred for 24 hours. The mixture was diluted with water (100 mL) and extracted with ether (100 mL), washed with brine, dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexxane with a gradient of 0-20% to give tert-butyl 3-[1-(3-fluorophenyl)-methylidene]piperidine-1-carboxylate (1.42 g).

Workup

  1. stirringthe mixture was stirred for 24 hours
  2. extractionextracted with ether (100 mL)
  3. washwashed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexxane with a gradient of 0-20%

Sources & evidence

ORD record
ord-9b94551b56014567851787861eadf205
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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