2-(4,4-difluoropiperidin-1-yl)-2-phenylacetonitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

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. the mixture heated to reflux for 2 hours concentrated in vacuo The residue was partitioned between water and CH2Cl2 the aqueous portion extracted 2×CH2Cl2 the organic portion dried (Na2SO4) concentrated in vacuo The resulting material was used without further purification