Ethylene Glycol → 5-(1,3-Dioxolan-2-YL)-2-fluoropyridine

Participants

Reaction Conditions

Reaction Steps

6-Fluoronicotinaldehyde (Asymchem Laboratories, Inc., Morrisville, N.C., 3.035 g, 24.26 mmol) was suspended in toluene (80 mL) and ethylene glycol (1.40 mL, 25.1 mmol) and p-toluenesulfonic acid (Acros Organics, Geel, Belgium, 12% in acetic acid, 0.15 mL) was added. The flask was fitted with a reflux condenser and placed in a preheated oil bath (120° C.) and stirred under nitrogen for 20 minutes. At this time, the reflux condenser was replaced with a Dean-Stark trap, and stirring was continued at 120° C. for 25 minutes. Then, the reaction was cooled and diluted with saturated sodium bicarbonate solution (20 mL) (before it had cooled to room temperature). The reaction was then diluted with water (20 mL) and EtOAc (30 mL). The layers were separated, and the aqueous phase was extracted with EtOAc. The organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and purified on a silica gel filter (about 3 inches, 40:1 DCM/MeOH to 30:1 DCM/MeOH) to afford 5-(1,3-dioxolan-2-yl)-2-fluoropyridine (3.858 g), which was taken on to the next step. MS (ESI pos. ion) m/z 170 (M+H)+.

Provenance & Evidence