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

Participants

Reaction Steps

To a suspension of NaBH4 (2.7 g, 72 mmol) in THF (150 mL) at −10° C. was added boron trifluoride etherate (9.1 mL, 72 mmol) and the solution was stirred for 15 minutes. Then a solution of 1-benzyl-4-(4-methoxyphenyl)-1,2,3,6-tetrahydropyridine (10 g, 36 mmol) in 100 mL tetrahydrofuran was added and the mixture was stirred for an additional hour. Next were sequentially added 25 mL of water, 25 mL of 10% aqueous sodium hydroxide, 50 mL of ethanol, and 12.8 mL of 30% aqueous hydrogen peroxide (125 mmol) and the final mixture was heated to reflux overnight. The mixture was allowed to cool and was then diluted with 200 mL of water and extracted with 300 mL of ethyl acetate. The organic layer was separated, dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was triturated with diethyl ether to yield 7.5 g (57%) (±)-rel-(3S,4S)-1-benzyl-4-(4-methoxyphenyl)piperidin-3-ol. LCMS (method A) RT 2.03 min, 81.5% AP, m/z 298.4 (M+H+), 1H NMR (300 MHz, DMSO-d6) δ ppm 7.28-7.35 (m, 5H) 7.14 (d, J=8.69 Hz, 2H) 6.83 (d, J=8.69 Hz, 2H) 4.43 (d, J=6.04 Hz, 1H) 3.51 (d, J=19.26 Hz, 4H) 3.33 (s, 3H) 2.97 (dd, J=10.01, 3.59 Hz, 1H) 2.81 (d, J=10.95 Hz, 1H) 2.19-2.29 (m, 1H) 1.96-1.98 (m, 1H) 1.78 (t, J=10.20 Hz, 1H) 1.58-1.68 (m, 2H).

Provenance & Evidence