Hydrogen Peroxide → trans-1-Benzyl-4-(4-methoxyphenyl)piperidin-3-ol

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Reaction Steps

To a suspension of sodium tetrahydroborate (2.7 g, 72 mmol) in THF (200 mL) 0° C. was added dropwise boron trifluoride etherate (8.8 mL, 70 mmol) under a nitrogen atmosphere and the resulting mixture was stirred for 30 minutes. Then was added 1-benzyl-4-(4-methoxyphenyl)-1,2,3,6-tetrahydropyridine (10 g, 36 mmol) (from S. Halazy et al WO 97/28140 (8/7/97)) dissolved in 100 mL of tetrahydrofuran. Stirring was continued at rt for 2 hours. The reaction was then quenched by the dropwise addition of 100 mL water. Next were added sequentially 100 mL ethanol, 100 mL 10% aqueous sodium hydroxide, and hydrogen peroxide (18 mL, 18 mmol) and the temperature was raised to reflux overnight. The reaction mixture was diluted with saturated aqueous ammonium chloride (200 mL), and extracted with ethyl acetate (500 mL). The organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure to give trans-1-benzyl-4-(4-methoxyphenyl)piperidin-3-ol (8.5 g, 24.6 mmol, 69% yield). LCMS (Method K) RT 1.99 min; m/z 298.0 (MH+).

Provenance & Evidence