Diethyl Ether → tert-Butyl 4-cyano-3,6-dihydropyridine-1(2H)-carboxylate

HRID 2267145Notes

Reaction equation

HRID 2267145 reaction equation
C(OCC)C.O=[C:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1.[C-:20]#[N:21].[Na+].C(=O)([O-])O.[Na+]>O>[C:20]([C:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH:8]=1)#[N:21]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 8929Sodium CyanideHCID 516892Sodium BicarbonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 68431027tert-Butyl 4-cyano-3,6-dihydropyridine-1(2H)-carboxylateYield 78.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Diethyl ether (15 ml) and 8 ml of water were added to 790 mg of tert-butyl 4-oxopiperidine-1-carboxylate, 216 mg of sodium cyanide and 672 mg of sodium hydrogen carbonate and the solution was stirred at room temperature for 1.5 hours. The resulting product was extracted with ether, washed with water and a saturated saline solution and dried over sodium sulfate. After the solvent was evaporated in vacuo, 10 ml of chloroform, 0.84 ml of triethylamine and 0.34 ml of methanesulfonyl chloride were added to the resulting residue followed by stirring at room temperature for 20 minutes. The reaction was stopped by water, the product was extracted with chloroform and the organic layer was washed with a saturated sodium hydrogen carbonate and a saturated saline solution and dried over sodium sulfate. The solvent was evaporated in vacuo, 10 ml of pyridine was added to the resulting residue and the mixture was stirred for one night under heating to reflux. After cooling to room temperature, the solvent was evaporated in vacuo followed by adding ethyl acetate and water. The organic layer washed with a saturated saline solution and dried over sodium sulfate and the solvent was evaporated in vacuo. The resulting residue was purified by a silica gel column chromatography (hexane/ethyl acetate=6/1) to give 650 mg of the title compound as a white solid.

Workup

  1. extractionThe resulting product was extracted with ether
  2. washwashed with water
  3. dry with materiala saturated saline solution and dried over sodium sulfate
  4. customAfter the solvent was evaporated in vacuo, 10 ml of chloroform, 0.84 ml of triethylamine and 0.34 ml of methanesulfonyl chloride
  5. additionwere added to the resulting residue
  6. stirringby stirring at room temperature for 20 minutes
  7. extractionthe product was extracted with chloroform
  8. washthe organic layer was washed with a saturated sodium hydrogen carbonate
  9. dry with materiala saturated saline solution and dried over sodium sulfate
  10. customThe solvent was evaporated in vacuo, 10 ml of pyridine
  11. additionwas added to the resulting residue
  12. stirringthe mixture was stirred for one night
  13. temperatureunder heating to reflux
  14. temperatureAfter cooling to room temperature
  15. customthe solvent was evaporated in vacuo
  16. additionby adding ethyl acetate and water
  17. washThe organic layer washed with a saturated saline solution
  18. dry with materialdried over sodium sulfate
  19. customthe solvent was evaporated in vacuo
  20. customThe resulting residue was purified by a silica gel column chromatography (hexane/ethyl acetate=6/1)

Sources & evidence

ORD record
ord-987096329b854623a0924a859c908562
Source dataset
uspto-grants-2010_12
Patent number
US07858800B2

Reaction notes

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