Methanol → (S)-2-methyl-N-((1S)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)ethyl)propane-2-sulfinamide

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence