Methyl iodide → 1,1-Dimethylethyl (3S)-3-methoxy-1-piperidinecarboxylate

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Reaction Steps

To a solution of 1,1-dimethylethyl (3S)-3-hydroxypiperidine-1-carboxylate (Preparation 127, 1.8 g, 9.2 mmol) in anhydrous tetrahydrofuran (40 ml) was added sodium hydride (60% dispersion in oil, 0.39 g, 9.2 mmol) in portions. The resulting mixture was stirred for 25 min then iodomethane (2.83 g, 20 mmol) was added dropwise and the reaction mixture was stirred for 17 h. The reaction mixture was diluted with ethyl acetate (200 ml) and washed with brine (5% solution, 200 ml). The aqueous layer, was extracted with ethyl acetate (2×50 ml) and the combined organic extracts were dried (MgSO4) and concentrated in vacuo. The resulting yellow oil was purified by flash chromatography on silica gel (100 g) eluting with dichloromethane:methanol (100:1 and then 50:1) to give a yellow oil. The trace of iodine was removed by dissolving the product in diethyl ether (60 ml) and washing with aqueous sodium metabisulphite (5% solution, 1×40 ml), water (2×40 ml) and aqueous sodium hydrogen carbonate (5% solution, 40 ml). The organic extracts were dried (MgSO4) and concentrated in vacuo to give the desired product as a colourless oil (1.43 g).

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