反应详情

温度

75 °C

To a solution of (R)-2-methylpropane-2-sulfinamide (6.9 g, 57.31 mmol) and Ti(OEt)4 (26.1 g, 114.62 mmol) in THF (200 mL) at RT was added 82 (14 g, 57.31 mmol). The reaction mixture was heated to 75° C. overnight. After MS analysis indicated complete conversion of 122, the mixture was cooled to RT and then to −48.0° C. L-Selectride (172 mL, 1M solution in THF) was added dropwise. The reaction mixture was warmed. When the reduction was complete the reaction mixture was cooled to 0° C. and MeOH was added dropwise until gas evolution was no longer observed. The crude reaction mixture was poured into an equal volume of rapidly stirred brine. The resulting suspension was filtered through a plug of Celite® and the filter cake was washed with EtOAc. The filtrate was washed with brine, and the brine layer was extracted with EtOAc, dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by SiO2 chromatography eluting with DCM/MeOH (20:1) to afford 10 g (50%) of (S)-2-methyl-N-((1S)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)ethyl)propane-2-sulfinamide (124) as yellow oil.

1. temperaturethe mixture was cooled to RT
2. customto −48.0° C
3. temperatureThe reaction mixture was warmed
4. temperaturewas cooled to 0° C.
5. customThe crude reaction mixture
6. filtrationThe resulting suspension was filtered through a plug of Celite®
7. washthe filter cake was washed with EtOAc
8. washThe filtrate was washed with brine
9. extractionthe brine layer was extracted with EtOAc
10. dry with materialdried (Na2SO4)
11. customevaporated under reduced pressure
12. customThe residue was purified by SiO2 chromatography
13. washeluting with DCM/MeOH (20:1)