Tetrahydrofuran → HCID 90424169, compound

Participants

Reaction Conditions

Reaction Steps

Separately, prepare a −78° C. solution of (2R)-1-[tert-butyl(diphenyl)silyl]oxy-3-[2-(hydroxymethyl)imidazol-1-yl]propan-2-ol (5.3 g; 1.0 equiv; 12.91 mmoles) in dichloromethane (25 mL). Add the in situ prepared iodinating reagent dropwise to the solution of (2R)-1-[tert-butyl(diphenyl)silyl]oxy-3-[2-(hydroxymethyl)imidazol-1-yl]propan-2-ol, with the orange color quickly fading to nearly colorless. Maintain the solution at −78° C. for 30 minutes, then allow it to warm to 0° C. and maintain for 10 minutes. Re-cool the solution to −78° C., and add tetrahydrofuran (100 mL) followed by 60% sodium hydride (1.14 g; 2.2 equiv; 28.40 mmoles). Slowly warm the solution to 0° C. over 30 minutes, and then to ambient temperature for 1 hour. Pour the mixture slowly into 50% saturated sodium bicarbonate solution and extract with dichloromethane (4×100 mL). Dry the combined organic extracts over magnesium sulfate, filter, and concentrate. Purify the crude product by column chromatography (10 to 100% ethyl acetate in hexanes) to afford the desired product contaminated with triphenylphosphine oxide. Further purify by SCX ion-exchange chromatography (10% methanol in dichloromethane to 10% (4N ammonia in methanol) in dichloromethane) to afford the desired tert-butyl-[[(6R)-6,8-dihydro-5H-imidazo[2,1-c][1,4]oxazin-6-yl]methoxy]-diphenyl-silane (1.86 g; 37%). MS (m/z): 393(M+1).

Provenance & Evidence