Tetrahydrofuran → HCID 90423419, compound

Participants

Reaction Conditions

Reaction Steps

Separately, prepare a −78° C. solution of 1-[tert-butyl(diphenyl)silyl]oxy-3-[2-(hydroxymethyl)imidazol-1-yl]propan-2-ol (9.4 g; 1.0 equiv; 22.89 mmoles) in dichloromethane (100 mL). Add the in situ prepared iodinating reagent dropwise to this solution 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. Recool the solution to −78° C., and add tetrahydrofuran (150 mL) followed by 60% sodium hydride (2.20 g; 2.4 equiv; 54.95 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-(6,8-dihydro-5H-imidazo[2,1-c][1,4]oxazin-6-ylmethoxy)-diphenyl-silane (5.96 g; 66%) as a colorless gum. MS (m/z): 393(M+1).

Provenance & Evidence