Hydrogen Bromide → HCID 66971095, compound

Participants

Reaction Steps

1-((1S,2R,4R)-bicyclo[2.2.1]heptan-2-yl)-4-(2-methoxyphenyl)piperidine (compound no. 397) (2.000 g, 6.21 mmol) was dissolved in acetic acid (33 mL) and treated with aq. HBr 48% (33 mL). After refluxing for 4 h the solvent was evaporated under reduced pressure, and the residue was azeotroped with dichloromethane (3×30 mL) to eliminate most of the acetic acid. Diethyl ether (100 mL) was added to the residue, and the mixture was shaken with saturated K2CO3 (100 mL) until most solids disappeared. The layers were separated, and the aqueous layer was extracted with diethyl ether (4×100 mL). The combined ethereal extracts were dried over Na2SO4 and concentrated. The crude product was dissolved in diethyl ether (40 mL) and treated with excess 1 N HCl in ether (20 mL). The pink precipitate was collected by filtration and dried under vacuum to provide 2-(1-((1S,2R,4R)-bicyclo[2.2.1]heptan-2-yl)piperidin-4-yl)phenol (compound no. 229) as a white solid. LC/MS (RP-C18, 10-99% CH3CN/0.05% TFA gradient over 5 min) m/z 272.0 [M+H]+, retention time 1.83 min.

Provenance & Evidence