Methyl morpholine oxide → (3S,5R)-3-methoxy-5-[((S)-1-methoxycarbonyl-ethylamino)-methyl]-morpholine-4-carboxylic acid tert-butyl ester

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Reaction Steps

Osmium tetroxide solution (2.5% in tert-butyl alcohol, 0.49 mL, 77 μmol) was added at 0° C. to a solution of (S)-3-allyloxy-2-tert-butoxycarbonylamino-propionic acid methyl ester (Org. Lett. 2007, 9, 3061; 1.00 g, 3.86 mmol) and 50% aq. 4-methylmorpholine-4-oxide solution (1.81 g, 7.71 mmol) in THF/water 2:1 (8 mL), then after 1 h sodium periodate (2.47 g, 11.6 mmol) was added. The ice bath was removed, then after 2 h the reaction mixture was treated with 10% aq. sodium sulfite solution (5.2 mL) and stirred for an additional 3 h, then poured upon water and extracted with EtOAc. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and evaporated. The residue [(3S,5R)-3-hydroxy-5-[((S)-1-methoxycarbonyl-ethylamino)-methyl]-morpholine-4-carboxylic acid tert-butyl ester] was dissolved in MeOH (5 mL), treated with toluene 4-sulfonic acid monohydrate (66 mg, 0.39 mmol), stirred for 1 h at room temperature, and concentrated in vacuo. The residue was redissolved in EtOAc and washed with 1 M aq. sodium hydrogencarbonate solution. The organic layer was dried over magnesium sulfate, filtered, and evaporated to afford crude (3S,5R)-3-methoxy-5-[((S)-1-methoxycarbonyl-ethylamino)-methyl]-morpholine-4-carboxylic acid tert-butyl ester (908 mg) as a brown oil. This was dissolved in DCM (10 mL), cooled to −78° C., then boron trifluoride etherate (928 mg, 6.54 mmol) and allyl trimethylsilane (560 mg, 4.90 mmol) were added, then after 2 h the reaction mixture was poured upon sat. aq. sodium hydrogencarbonate solution. The organic layer was dried over magnesium sulfate, filtered, and evaporated. Chromatography (SiO2; heptane/EtOAc 70:30) afforded the title compound (601 mg, 55%). Colourless oil, MS: 308.1 (M+Na)+.

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