Methanol → 1-Benzyl-4,4-dimethoxypiperidin-3-ol

Participants

Reaction Steps

1-Phenylmethyl-4-piperidone (18.92g, 100 mmol) in 40 ml of methanol was added slowly over a period of 15 minutes to a solution of potassium hydroxide (16.83g, 100 mmol) in 150 ml of methanol at 0° C. Iodobenzene diacetate (35.43 g, 110 mmol) was then added to the mixture in portions over a period of thirty minutes. The reaction mixture was stirred at room temperature overnight. The mixture was then concentrated under vacuum to remove the excess of methanol and the crude residue was diluted with a mixture of water (500 ml) and dichloromethane (300 ml). The dichloromethane layer was separated and the aqueous phase was again extracted with 150ml of dichloromethane. The combined organic layers were dried over sodium sulfate and concentrated under vacuum. The crude residue was dissolved in 100 ml of hexane and crystallized. The solid was washed with 30ml of hexane to yield the intermediate 1-phenylmethyl-3-hydroxy-4,4-dimethoxypiperidine (3b, 6.48 g, 25.8%).

Provenance & Evidence