Ethanol → 1-(6-Ethoxy-pyridin-3-yl)-4,4-difluoro-cyclohexanecarbonitrile

HRID 512156Notes

Reaction equation

HRID 512156 reaction equation
[Na].Br[C:3]1[N:8]=[CH:7][C:6]([C:9]2([C:17]#[N:18])[CH2:14][CH2:13][C:12]([F:16])([F:15])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[CH2:19]([OH:21])[CH3:20]>>[CH2:19]([O:21][C:3]1[N:8]=[CH:7][C:6]([C:9]2([C:17]#[N:18])[CH2:14][CH2:13][C:12]([F:16])([F:15])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)[CH3:20]

Participants

4

Reactant 3

HCID 702EthanolHCID 5360545SodiumHCID 86716177HCID 86716177, compound

Product 1

HCID 867161791-(6-Ethoxy-pyridin-3-yl)-4,4-difluoro-cyclohexanecarbonitrileYield 49%

Conditions

Temperature
70 °C

Procedure

Sodium metal (229 mg, 9.96 mmol) was added to ethanol (5 mL) at room temperature. To this solution was added 1-(6-bromo-pyridin-3-yl)-4,4-difluoro-cyclohexanecarbonitrile (300 mg, 1.00 mmol) and the reaction was heated at 70° C. for 6 hours. After cooling to room temperature the volatiles were removed under reduced pressure. The residue was diluted with water and extracted with AcOEt (2×50 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography to afford 1-(6-ethoxy-pyridin-3-yl)-4,4-difluoro-cyclohexanecarbonitrile (130 mg, 49%). LC-MS (m/z) 241.4 (MH+). 1H NMR (400 MHz, CDCl3) δ ppm 8.30 (d, J=2.7 Hz, 1 H), 7.66 (dd, J=8.8, 2.7 Hz, 1 H), 6.78 (d, J=8.8, Hz, 1 H), 4.38 (q, J=7.1, Hz, 2 H), 2.07-2.42 (m, 8 H), 1.41 (t, J=7.1, Hz, 3 H).

Workup

  1. temperatureAfter cooling to room temperature the volatiles
  2. customwere removed under reduced pressure
  3. additionThe residue was diluted with water
  4. extractionextracted with AcOEt (2×50 mL)
  5. dry with materialThe combined organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-fa3d9cf5d7e946d1ae61a93ae3a87cc6
Source dataset
uspto-grants-2015_08
Patent number
US09102591B2

Reaction notes

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