Sodium hydride → 2-(6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)acetonitrile

HRID 887767Notes

Reaction equation

HRID 887767 reaction equation
[C:1]([CH2:3]P(=O)(OCC)OCC)#[N:2].[H-].[Na+].[CH:14]1[C:19]2[C:20](=O)[CH2:21][CH2:22][C:18]=2[CH:17]=[CH:16][N:15]=1>O1CCCC1.C(=O)([O-])O.[Na+]>[CH:14]1[C:19]2[CH:20]([CH2:3][C:1]#[N:2])[CH2:21][CH2:22][C:18]=2[CH:17]=[CH:16][N:15]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 75676Diethyl (cyanomethyl)phosphonateHCID 151488235,6-Dihydro-7H-cyclopenta[c]pyridin-7-one

Product 1

HCID 591458942-(6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)acetonitrileYield 62%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of diethyl cyanomethylphosphonate (346 mg, 1.95 mmol) in tetrahydrofuran (10 mL) was added 60% sodium hydride (54.0 mg, 1.35 mmol) under ice-cooling, and the mixture was stirred at room temperature for 30 min. The mixture was added to a solution of 5,6-dihydro-7H-cyclopenta[c]pyridin-7-one (130 mg, 0.976 mmol) in tetrahydrofuran (5 mL) under ice-cooling, and the mixture was stirred for 15 min. The reaction solution was diluted with saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=50/50→80/20). To a solution of the purified product in methanol (10 mL) was added palladium-carbon powder (30 mg), and the mixture was stirred under a hydrogen atmosphere at room temperature for 4 hr. The catalyst was filtered off, and the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→70/30) to give the title compound (95.0 mg, yield 62%).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringthe mixture was stirred for 15 min
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialThe extract was dried over anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=50/50→80/20)
  8. additionTo a solution of the purified product in methanol (10 mL) was added palladium-carbon powder (30 mg)
  9. stirringthe mixture was stirred under a hydrogen atmosphere at room temperature for 4 hr
  10. filtrationThe catalyst was filtered off
  11. customthe filtrate was evaporated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→70/30)

Sources & evidence

ORD record
ord-bfd8babdc7e246e88038eb3153875584
Source dataset
uspto-grants-2012_08
Patent number
US08247429B2

Reaction notes

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