Sodium hydride → tert-Butyl 4-(2,5-difluoro-4-nitrobenzylidene)piperidine-1-carboxylate

HRID 515307Notes

Reaction equation

HRID 515307 reaction equation
[F:1][C:2]1[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[C:14]([F:20])=[CH:13][C:3]=1[CH2:4]P(=O)(OCC)OCC.O=[C:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1.[H-].[Na+]>O1CCCC1>[F:1][C:2]1[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[C:14]([F:20])=[CH:13][C:3]=1[CH:4]=[C:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 86670952HCID 86670952, compound

Product 1

HCID 67193923tert-Butyl 4-(2,5-difluoro-4-nitrobenzylidene)piperidine-1-carboxylateYield 31.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diethyl 2,5-difluoro-4-nitrobenzylphosphonate (0.67 g, 2.17 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (0.43 g, 2.17 mmol) were stirred in tetrahydrofuran (8.3 mL) and cooled in an ice bath. Sodium hydride (0.133 g, 2.82 mmol) was added then the reaction was taken off ice bath and stirred for 4 hours at room temperature. The reaction was quenched with water and extracted with dichloromethane, dried (magnesium sulphate), filtered and evaporated under reduced pressure. The crude material was purified by silica chromatography using a dichloromethane solvent system. The solid obtained was triturated with heptane to give the title compound as a yellow solid (0.24 g). 1H NMR (CDCl3, 400 MHz): δ 7.80 (dd, 1H), 7.12 (dd, 1H), 6.24 (s, 1H), 3.54 (t, 2H), 3.45 (t, 2H), 2.40 (t, 2H), 2.56 (t, 2H), 1.48 (s, 9H)

Workup

  1. temperaturecooled in an ice bath
  2. customThe reaction was quenched with water
  3. extractionextracted with dichloromethane
  4. dry with materialdried (magnesium sulphate)
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe crude material was purified by silica chromatography
  8. customThe solid obtained
  9. customwas triturated with heptane

Sources & evidence

ORD record
ord-8fa98e5324a14f0f9d03efdabaae0626
Source dataset
uspto-grants-2015_08
Patent number
US09108939B2

Reaction notes

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