反应详情

Borane dimethyl sulfide complex (2 mol/L in diethyl ether, 4.64 mL) is added dropwise to a solution of 8-[(S)-1-(4-bromo-phenyl)-ethyl]-6-oxa-8-aza-spiro[4.5]dec-2-en-7-one (2.60 g) in tetrahydrofuran (30 mL) chilled in an ice bath. The cooling bath is removed and the solution is stirred at room temperature overnight. The solution is then chilled again in an ice bath and 4 M aqueous NaOH solution (2.1 mL) is added followed by the dropwise addition of hydrogen peroxide (35% in water, 6 mL). The cooling bath is removed and the mixture is warmed to 40° C. and stirred at this temperature for 1 h. The mixture is diluted with water and extracted with diethyl ether. The combined extracts are washed with water, dried (Na2SO4), and concentrated. The residue is chromatographed on silica gel (methanol/ethyl acetate 0:1→4:1) to afford a mixture of the four title compounds which is submitted to SFC (Supercritical Fluid Chromatography) on chiral phase (column: phenomenex LUX 2A, 250×20 mm, 5 μM; eluent: isopropanol containing 0.2% diethylamine/sc carbon dioxide 25:75; flow: 60 mL/min) to give the four isomers in separate fractions.

1. temperaturechilled in an ice bath
2. customThe cooling bath is removed
3. temperatureThe solution is then chilled again in an ice bath
4. addition4 M aqueous NaOH solution (2.1 mL) is added
5. additionfollowed by the dropwise addition of hydrogen peroxide (35% in water, 6 mL)
6. customThe cooling bath is removed
7. temperaturethe mixture is warmed to 40° C.
8. stirringstirred at this temperature for 1 h
9. additionThe mixture is diluted with water
10. extractionextracted with diethyl ether
11. washThe combined extracts are washed with water
12. dry with materialdried (Na2SO4)
13. concentrationconcentrated
14. customThe residue is chromatographed on silica gel (methanol/ethyl acetate 0:1→4:1)
15. customto afford
16. additiona mixture of the four title compounds which
17. customto give the four isomers in separate fractions