2-fluoro-6-piperidin-1-ylbenzonitrile

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: 2,6-Difluorobenzonitrile (250 mg; 1.8 mmol) and piperidine (145 mg; 1.7 mmol) were mixed in DMF (5 mL) for 3 hours at RT. The solvent is removed under vacuum, and the resulting oil is dried under vacuum at 30° C. overnight to yield 152 milligrams of 2-fluoro-6-(piperidin-1-yl)benzonitrile. The solvent is removed under vacuum the resulting oil is dried under vacuum at 30° C. overnight

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

Procedure: To a solution of phenol (415 mg, 4.5 mmol) in 60 mL of DMF was added NaH (60%, 6.0 mmol) at 0° C. The reaction was stirred for 1 h, then 2-fluoro-6-(piperidin-1-yl)benzonitrile (CAS#646989-68-6) (612 mg, 3.0 mmol) was added and the reaction stirred for 48 h at RT. The reaction mixture was then diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, then concentrated in vacuo. Purification by normal phase silica gel column chromatography (EtOAc/heptane) provided 2-phenoxy-6-(piperidin-1-yl)benzonitrile as an off-white solid. the reaction stirred for 48 h at RT extracted with EtOAc The combined organic layers were washed with brine dried over Na2SO4 concentrated in vacuo Purification by normal phase silica gel column chromatography (EtOAc/heptane)

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

Procedure: 2,6-Difluorobenzonitrile (250 mg; 1.8 mmol) and piperidine (145 mg; 1.7 mmol) were mixed in DMF (5 mL) for 3 hours at RT. The solvent is removed under vacuum, and the resulting oil is dried under vacuum at 30° C. overnight to yield 152 milligrams of 2-fluoro-6-(piperidin-1-yl)benzonitrile. The solvent is removed under vacuum the resulting oil is dried under vacuum at 30° C. overnight