Hexane → 4-[2-(Hydroxyethyl)phenyl]-1-benzylpiperidin-4-ol

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Reaction Steps

To a solution of 2-bromophenyl ethyl alcohol (1.9 g, 9.6 mmol) in tetrahydrofuran (25 ml) was added 1.6 M n-butyl lithium solution in n-hexane (14 ml, 23 mmol) at −60° C. After stirring for 30 min a solution of 1-benzyl-4-piperidone (2.6 g, 14 mmol) in tetrahydrofuran (10 ml) was added over a period of 15 min at −40° C. The cooling bath was removed and the reaction mixture was stirred for 72 h at room temperature. The mixture was quenched with saturated aqueous ammonium chloride solution (30 ml). Basification to pH 11 with 2 M aqueous sodium carbonate solution (50 ml) was followed by extraction with three 100-ml portions of tert-butyl methyl ether. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. Volatile impurities were removed by kugelrohrdistillation at 170° C. and 1-2 mbar. Flash chromatography of the residual crude product with dichloromethane/methanol as eluent gave the title compound (2.3 g, 53%) as dark brown oil. MS m/e: 312 (M+H+).

Provenance & Evidence