反应详情

To a solution of 3-((S)-3-allyl-6-cyclohexyl-2-oxo-piperidin-1-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (less polar diastereomer from previous step) (200 mg, 0.45 mmol, 1.0 equiv) in acetone (3.0 mL) at 0° C. was added N-methylmorpholine oxide (160 mg, 1.36 mmol, 3 equiv), water (1.0 mL) and OsO4 (230 mg, 0.02 mmol, 0.05 equiv). The reaction mixture was stirred at room temperature for 1 hour. The solution was partitioned between brine and EtOAc. The phases were separated and the organic layer was dried over Na2SO4, and concentrated under vacuum. The residue was dissolved in THF/water (3.0 mL/1.0 mL). To the solution was added NaIO4 (194 mg, 0.9 mmol, 2 equiv), and the resulting mixture was stirred at room temperature for 30 minutes, after which another portion of NaIO4 (0.5 equiv) was added. After stirred at room temperature for 30 minutes, the mixture was partitioned between brine and EtOAc. The organic layer was separated, dried over Na2SO4, and concentrated. The residue was dissolved in EtOH (3.0 ml) and the solution was cooled at 0° C. To the solution was added NaBH4 and the mixture was stirred at 0° C. for 15 minutes. The reaction was quenched by addition of water (2.0 mL) and EtOAc (10.0 mL). The organic layer was separated, dried over Na2SO4, and concentrated. The residue was purified by silica gel column chromatography, Heptane/EtOAc 1/1 to give 123 mg of the product (yield 60%). MS: 446 [M+H+]

1. customThe solution was partitioned between brine and EtOAc
2. customThe phases were separated
3. dry with materialthe organic layer was dried over Na2SO4
4. concentrationconcentrated under vacuum
5. dissolutionThe residue was dissolved in THF/water (3.0 mL/1.0 mL)
6. stirringthe resulting mixture was stirred at room temperature for 30 minutes
7. stirringAfter stirred at room temperature for 30 minutes
8. customthe mixture was partitioned between brine and EtOAc
9. customThe organic layer was separated
10. dry with materialdried over Na2SO4
11. concentrationconcentrated
12. dissolutionThe residue was dissolved in EtOH (3.0 ml)
13. temperaturethe solution was cooled at 0° C
14. additionTo the solution was added NaBH4
15. stirringthe mixture was stirred at 0° C. for 15 minutes
16. customThe reaction was quenched by addition of water (2.0 mL) and EtOAc (10.0 mL)
17. customThe organic layer was separated
18. dry with materialdried over Na2SO4
19. concentrationconcentrated
20. customThe residue was purified by silica gel column chromatography, Heptane/EtOAc 1/1