Methyl iodide → (R)-tert-Butyl 3-methoxypiperidine-1-carboxylate

To a solution of 1,1-dimethylethyl (3R)-3-hydroxypiperidine-1-carboxylate (Preparation 128, 1.6 g, 7.95 mmol) in anhydrous tetrahydrofuran (35 ml) was added sodium hydride (60% dispersion in oil, 0.32 g, 7.95 mmol) in portions. The resulting mixture was stirred for 25 min then iodomethane (2.27 g, 16 mmol) was added dropwise and the reaction mixture was stirred for 17 h. The reaction mixture was diluted with ethyl acetate (150 ml) and washed with brine (5% solution, 150 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 (70 g) eluting with dichloromethane:methanol (100:1 and then 50:1) to give a yellow oil (1.68 g). The trace of iodine was removed by dissolving the product in ethyl acetate (50 ml) and washing with aqueous sodium metabisulphite (5% solution, 2×35 ml), water (35 ml) and aqueous sodium hydrogen carbonate (5% solution, 35 ml). The organic extracts were dried (MgSO4) and concentrated in vacuo to give the desired product as a colourless oil (1.62 g).

1. stirringthe reaction mixture was stirred for 17 h
2. washwashed with brine (5% solution, 150 ml)
3. extractionThe aqueous layer was extracted with ethyl acetate (2×50 ml)
4. dry with materialthe combined organic extracts were dried (MgSO4)
5. concentrationconcentrated in vacuo
6. customThe resulting yellow oil was purified by flash chromatography on silica gel (70 g)
7. washeluting with dichloromethane:methanol (100:1

ORD record

ord-1734476256eb4d65b217c58f38a7510c

Source dataset

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07494992B2