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

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)+.

1. customThe ice bath was removed
2. additionafter 2 h the reaction mixture was treated with 10% aq. sodium sulfite solution (5.2 mL)
3. additionpoured upon water
4. extractionextracted with EtOAc
5. washThe organic layer was washed with brine
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. customevaporated
9. dissolutionThe residue [(3S,5R)-3-hydroxy-5-[((S)-1-methoxycarbonyl-ethylamino)-methyl]-morpholine-4-carboxylic acid tert-butyl ester] was dissolved in MeOH (5 mL)
10. stirringstirred for 1 h at room temperature
11. concentrationconcentrated in vacuo
12. dissolutionThe residue was redissolved in EtOAc
13. washwashed with 1 M aq. sodium hydrogencarbonate solution
14. dry with materialThe organic layer was dried over magnesium sulfate
15. filtrationfiltered
16. customevaporated

ORD record

ord-2b56f7ab204948a78ca46d6af1308c0c

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08471004B2