Hydrochloric Acid → 1-Carbethoxy-4-hydroxy-4-[2-(4-methylphenylsulfanyl)phenyl]piperidine

Participants

Reaction Conditions

Reaction Steps

In anhydrous equipment under a nitrogen atmosphere was stirred a mixture of 2-(4-tolylsulfanyl)-phenyl bromide (600 g, 2.15 mol) in heptanes (4.5 L) at room temperature (25° C.). n-Bu-lithium (10 M, 236 mL) solution in heptane was then added by canulation. After stirring at room temperature for 30 minutes the reaction mixture was cooled to −50° C. before a solution of carbetoxypiperidone in THF (1.5 L) was added dropwise while maintaining the temperature under −40° C. Once the addition was completed, reaction was allowed to warm to 0° C. before dilute HCl (1 L) was added maintaining the temperature below 10° C. Once addition was complete reaction was stirred for a further 15 minutes before phases where allowed to separate. Phases were separated, the water layer was extracted with ethyl acetate (1 L) and the organic layers combined. The combined organic layer was washed with NaCl solution (15%) (1 L), dried over magnesium sulphate, evaporated to dryness and slurried in diethyl ether (250 mL) for 30 minutes, filtered and dried at 40° C. in a vacuum oven. Yield 55-60%.

Provenance & Evidence