Water → 1-(3-Chloro-4-fluorobenzyl)piperidin-2-one

Participants

Reaction Steps

Valerolactam (60 g) was dissolved in MTBE (1.5 L) at room temperature. To this solution was added Bu4NSO4 (4.9 g) as a phase transfer catalyst. The cloudy solution was stirred at room temperature for 5 minutes. Then, NaOH (50 wt %; 300 mL) was slowly added as to keep the internal temperature below 30° C. 3-Chloro-4-fluorobenzyl bromide (108.3 g) was then added slowly to this biphasic mixture, again as to keep the internal temperature under control. The reaction was then aged for 4 hours at room temperature. At this time LC showed the reaction to be complete. Water (500 mL) was then added. After phase cut, the organic layer was washed with brine (300 mL), dried under MgSO4 followed by solvent switch to heptane (400 mL). The slurry obtained was stirred at room temperature. for 1 hour and then filtered to afford the title product.

Provenance & Evidence