Tetrahydrofuran → (-)-trans-4-(4'-Fluorophenyl)-3-hydroxymethyl-N-methylpiperidine

Participants

Reaction Steps

Compound E4 (34 g) in toluene (150 ml) was added slowly to a slurry of lithium aluminium hydride (10 g) in a tetrahydrofuran (50 ml)/toluene (150 ml) mixture, maintaining the temperature at 0°-5° C. under nitrogen. (Commercially available solutions of lithium aluminium hydride in tetrahydrofuran/toluene have also been used successfully). The mixture was stirred for a further 1-5 hours and then allowed to warm up to 15°-25° C. overnight. The excess lithium aluminium hydride was destroyed by the carefully controlled addition of water (10 ml), dilute 15% sodium hydroxide (10 mls) and water (30 ml). The solids were then removed by filtration and reslurried in toluene (100 ml). The combined rich toluene layers were concentrated to a low volume (75 ml) and poured into petroleum ether [100°-120°] (25 ml). After stirring for 8-24 hours the product was isolated by filtration, washed with petroleum ether (10 ml) and dried.

Provenance & Evidence