Dimethyl Sulfoxide → 1,2-Dibenzyl 3-(tert-butyl) (2S,3S)-5-oxopiperidine-1,2,3-tricarboxylate

Temperature

78 °C

To an oven-dried 5 mL conical vial equipped with a magnetic stir bar and under a nitrogen gas atmosphere was placed oxalyl chloride (0.080 mL, 0.92 mmol) and methylene chloride (0.7 mL). The solution was cooled to 78° C. prior to the dropwise addition of dimethyl sulfoxide (0.080 mL, 1.13 mmol) in methylene chloride (0.3 mL). After stirring the solution for 45 min, a solution of 1,2-dibenzyl 3-tert-butyl(2S,3S)-5-hydroxypiperidine-1,2,3-tricarboxylate (266 mg, 0.567 mmol) in methylene chloride (1 mL) was added dropwise and the solution was allowed to gradually warm to ca. 0° C. over 1.5 h. The reaction mixture was cooled to 78° C. prior to the dropwise addition of triethylamine (0.240 mL, 1.72 mmol) and stirring was continued for 3 h with gradual warming to ca. 0° C. The reaction was quenched by the dropwise addition of 5% citric acid (2 mL) and diluted with methylene chloride (15 mL). The organic layer was washed with brine (2×5 mL), dried (NaSO4), and concentrated in-vacuo to afford 264 mg (100%) of the desired ketone as a sticky yellow oil. LCMS (ESI): 490 (M+Na+)

1. customTo an oven-dried 5 mL conical vial equipped with a magnetic stir bar and under a nitrogen gas atmosphere
2. temperatureto gradually warm to ca. 0° C. over 1.5 h
3. temperatureThe reaction mixture was cooled to 78° C.
4. stirringstirring
5. waitwas continued for 3 h
6. temperaturewith gradual warming to ca. 0° C
7. customThe reaction was quenched by the dropwise addition of 5% citric acid (2 mL)
8. additiondiluted with methylene chloride (15 mL)
9. washThe organic layer was washed with brine (2×5 mL)
10. dry with materialdried (NaSO4)
11. concentrationconcentrated in-vacuo

ORD record

ord-f6021f85a70046e68ee4b4afebfe5af7

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09440958B2