Hydrochloric Acid → HCID 68983099, compound

Participants

Reaction Conditions

Reaction Steps

A 22 L 3-neck RBF equipped with a cooling bath, an addition funnel, mechanical stirrer, thermocouple and nitrogen bubbler was purged with nitrogen for at least ten minutes. The flask was charged with 0.612 kg (2.43 mol) 1-[(R)-3-(3-amino-5-fluoro-phenoxy) -piperidin-1-yl]-ethanone and 12.2 L (20 vol) ethyl acetate. The solution was cooled to 0±5° C. in an ice/brine bath, and 1.46 L (2.92 mol) 2M HCl in ether was added dropwise for 20 minutes, maintaining the internal temperature below 10° C. The solution stirred for 2 hours at 0±5° C., and the solid was filtered under a nitrogen atmosphere and rinsed with 6.0 L (10 vol) ethyl acetate. The solid was dried at 50±5° C. under vacuum for 2 days to afford 693 g of 1-[(R)-3-(3-amino-5-fluoro-phenoxy)-piperidin-1-yl]-ethanone HCl salt in 99% yield as an off-white solid (theoretical yield=0.700 kg, purity=94.2% and 97.6% ee).

Provenance & Evidence