Hydrochloric Acid → 4-(2-Bromo-5-fluorophenoxy)piperidine

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 4-(2-bromo-5-fluorophenoxy)piperidine-1-carboxylate from Step 1, Method (i), was dissolved in ethanol (200 mL), cooled to −78° C. and treated with 4 N HCl in dioxane (450 mL). The reaction was warmed and stirred overnight at room temperature. The solvent was removed under reduced pressure and the mixture partitioned between 1 N NaOH (750 mL) and a 1:1 mixture of ether-hexane. After several extractions, the organics layers were combined and evaporated to dryness. The crude material was dissolved in heptane (1 L) and a white precipitate was filtered and discarded. The heptane layer was diluted with ether and treated with 4 N HCl in dioxane (100 mL). The resulting precipitate was collected by filtration and washed three times with a 1:1 mixture of ether-hexane. The salt was partitioned again between 1 N NaOH (500 mL) and a 1:1 mixture of ether-hexane. After several extractions, the organic layers were combined, washed with brine, dried over magnesium sulfate, filtered and evaporated. The crude material was dissolved into heptane (2 L) and washed four times with 1 N NaOH (250 mL). The organic layer was washed with brine, dried over magnesium sulfate, filtered and evaporated to give the title compound as colorless oil.

Provenance & Evidence