反应详情

温度

-50 °C

A solution of diisobutylaluminium hydride in tetrahydrofuran (1M, 50 mL) was added dropwise to a stirred solution of (2S)-3-[[(1,1-dimethylethyl)diphenylsilyl]oxy]-N-methoxy-N,2-dimethyl-propanamide (Example 136a, 6.2 g) in tetrahydrofuran (40 mL) at 0° C. The mixture was stirred for 30 minutes and poured onto a mixture of ethyl acetate (250 mL) and 2M hydrochloric acid (100 mL). The organic phase was washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to give the crude aldehyde. Tetrahydrofuran (30 mL) was added followed by (R)-(+)-2-methyl-2-propanesulfinamide (2.6 g) and titanium ethoxide (10 mL). The mixture was stirred at room temperature for 90 min., then diluted with ethyl acetate (300 mL) and quenched with brine (100 mL). The mixture was stirred for 1 h. The organic phase was separated, dried (Na2SO4), filtered through a pad of Celite and concentrated in vacuo to give the crude sulfinimine, which was dissolved in dry dichloromethane (90 mL) and the solution was cooled to −50° C. A solution of phenylmagnesium bromide in diethyl ether (3M, 13 mL) was added dropwise and the reaction mixture was warmed up to 0° C. over 3 h, quenched with sat. aqueous NH4Cl (150 mL) and extracted into dichloromethane. The organic phase was dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified (SiO2 chromatography eluting with iso-hexane:ethyl acetate (0-100%)) to give the subtitle compound (5.2 g).

1. washThe organic phase was washed with brine
2. dry with materialdried (Na2SO4)
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customto give the crude aldehyde
6. stirringThe mixture was stirred at room temperature for 90 min.
7. customquenched with brine (100 mL)
8. stirringThe mixture was stirred for 1 h
9. customThe organic phase was separated
10. dry with materialdried (Na2SO4)
11. filtrationfiltered through a pad of Celite
12. concentrationconcentrated in vacuo
13. customto give the crude sulfinimine, which
14. temperaturethe reaction mixture was warmed up to 0° C. over 3 h
15. customquenched with sat. aqueous NH4Cl (150 mL)
16. extractionextracted into dichloromethane
17. dry with materialThe organic phase was dried (Na2SO4)
18. filtrationfiltered
19. concentrationconcentrated in vacuo
20. customThe residue was purified
21. wash(SiO2 chromatography eluting with iso-hexane:ethyl acetate (0-100%))