Acetic Acid → (4,4-Difluoropiperidin-1-yl)(phenyl)acetonitrile

HRID 1943033Notes

Reaction equation

HRID 1943033 reaction equation
[CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:9][C:10]1([F:16])[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.[C-:17]#[N:18].[Na+].C(O)(=O)C>CO>[F:9][C:10]1([F:16])[CH2:15][CH2:14][N:13]([CH:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:17]#[N:18])[CH2:12][CH2:11]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 240BenzaldehydeHCID 8929Sodium CyanideHCID 27583524,4-Difluoropiperidine

Product 1

HCID 53418752(4,4-Difluoropiperidin-1-yl)(phenyl)acetonitrile

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Benzaldehyde (1.284 ml, 12.63 mmol), 4,4-difluoropiperidine (1.53 g, 12.63 mmol), and NaCN (0.619 g, 12.63 mmol) were combined in MeOH (20 ml). Acetic acid (0.759 ml, 13.26 mmol) was added dropwise over 30 min via syringe pump and the mixture heated to reflux for 2 hours. The reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was partitioned between water and CH2Cl2, the aqueous portion extracted 2×CH2Cl2, and the organic portion dried (Na2SO4) and concentrated in vacuo. The resulting material was used without further purification.

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 2 hours
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned between water and CH2Cl2
  5. extractionthe aqueous portion extracted 2×CH2Cl2
  6. dry with materialthe organic portion dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe resulting material was used without further purification

Sources & evidence

ORD record
ord-45162c75f6e34e56844dbd9ab2c14167
Source dataset
uspto-grants-2013_03
Patent number
US08389720B2

Reaction notes

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