Benzyl chloroformate → HCID 21936871, compound

Participants

Reaction Conditions

Reaction Steps

A 2-L, three-necked, round-bottomed flask equipped with a mechanical stirrer and two addition funnels was charged with 4-cyclohexyl-4-piperidinecarboxylic acid hydrochloride (8-3) (157.9 g, 0.637 mol), 1 L of dioxane, and 255 mL of 5 N NaOH solution. The mixture was cooled at about 5° C., and then benzyl chloroformate (92 mL, 0.643 mmol) and 127 mL of 5 N NaOH solution were added dropwise simultaneously via two separate addition funnels while maintaining the temperature at or below 10° C. The reaction was monitored by TLC and, upon completion, the resulting mixture was diluted with 1 L of water and concentrated. The residue was diluted with 2 L of water and the pH was adjusted to about 12 using 5 N NaOH solution. The mixture was then extracted with 1 L of ethyl acetate. The aqueous layer was acidified to pH 1.5-2.0 using 2 N HCl solution, and extracted with three 1-L portions of ethyl acetate. The combined organic layers were washed with 1 L of saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated to give 165 g of title compound 8-4 as a white solid.

Provenance & Evidence