Hydrochloric Acid → (+)-4-[(4-Fluorophenoxy)phenyl]methyl-piperidine

Participants

Reaction Conditions

Reaction Steps

The alcohol prepared above (2.7 g, 9.3 mmol) dissolved in DMSO (25 mL) was added over an NaH (60%, 0.6 g) suspension in DMSO (5 mL). Potassium benzoate (1.53 g, 9.63 mmol) and 1,4-difluorobenzene (1.3 mL, 11.9 mmol) were added and the mixture was heated (70-75° C.) until the starting substance disappeared. The reaction mixture was poured into water and saturated aqueous NaCl solution, and extracted with ether. The oil obtained was refluxed with a mixture of methanol (40 mL) and an aqueous hydrochloric acid (40 mL) solution for 1 h. Isolation of the product using the customary methodology provided (+)-4-[(4-fluorophenoxy)phenyl]methyl-piperidine as an oil in a 54% yield. Treatment of 0.5 g (1.75 mmol) of this oil with D-dibenzoyltartaric acid in ethanol (96%, 30 mL) provided a precipitate which was filtered (m.p.=198-199° C.). The aminoether was released yielding a white solid with a 96% ee, m.p.=102-104° C., and [α]546+15, c=0.105, CHCl3).

Provenance & Evidence