Imidazole → 6-Chloro-3,4-dihydro-2-[4-[2-(t-butyldiphenylsiloxy)ethyl]phenyl]-4-hydroxy-2H-thieno[3,2-e]-1,2-thiazine 1,1-dioxide

Participants

Reaction Steps

The product from Step B (11.5 g, 0.032 mol) was added to DMF (100 mL) containing imidazole (5.44 g, 0.08 mol) and t-butyldiphenylsilyl chloride (9.34 mL, 0.035 mol) and stirred at room temperature for 18 hr. The reaction mixture was evaporated to dryness and the residue was suspended in methylene chloride and filtered. The filtrate was concentrated and chromatographed (silica, methylene chloride) to provide a solid which was dissolved in THF (200 mL) and cooled to 5° C. A solution of pyridinium bromide perbromide (11.23 g, 0.035 mol) in THF (50 mL) was added dropwise and this mixture was stirred at 5° C. for 1 hr, at ambient temperature for 1 hr, and then evaporated to dryness. The residue was suspended in ethanol (150 mL) and cooled to 5° C. followed by the addition of sodium borohydride (3.59 g, 95 mmol). The reaction mixture was maintained at room temperature for 1 hr and then heated at reflux temperature for 1.5 hr. Water was carefully added and the ethanol evaporated. The aqueous mixture was neutralized and extracted with ethyl acetate (2×200 mL). The combined extracts were dried (MgSO4) and evaporated to a residue which was purified by column chromatography (silica, 15% ethyl acetate/hexane) to provide an amber syrup (8.2 g, 44%).

Provenance & Evidence