Oxygen → HCID 86695134, compound

Participants

Reaction Steps

For the preparation of the starting material compound 43.1, please refer to Example 43. A 50-mL three necked round-bottom flask, purged and maintained with an inert atmosphere of nitrogen, was charged with a solution of tert-butyl N-methyl-N-(4-[[(3R)-3-(2-oxoethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yl]oxy]cyclohexyl)carbamate (500 mg, 1.12 mmol, 1.00 equiv) in 10 mL of distilled THF. Et3B (11.2 mL, 1N) was added slowly at 0° C. over 20 min. Then t-BuOOH (1.225 mL) was added dropwise to the mixture at the same temperature. After being stirred for 10 min, the mixture was allowed to warmed to room temperature and stirring was continued for an additional period during which the reaction proceeded to completion (Caution: Triethylborane, a liquid pyrophoric toward oxygen, should be handled so as to avoid exposure to air. The addition of tert-butyl hydroperoxide to trialkylboranes may lead to highly exothermic reactions and gas evolution. We encountered no violent reaction with the present procedures, but special care is advised.) The reaction mixture was treated with 28% NH4OH and extracted with CH2Cl2. (A 28% NH4OH solution allows the removal of unidentified polar materials possibly derived from Et3B. Removal of polar byproducts in the crude mixture, detectable on an iodine/silica gel TLC plate, may otherwise be difficult. The crude mixture must thus be washed with 28% NH4OH for adequate purification.) The extracts were washed with saturated aqueous NaHSO3 and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5) to provide tert-butyl N-(4-[[(3R)-3-[(2S)-2-hydroxy-2-[(2S)-oxolan-2-yl]ethyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (230 mg, 40%) as a colorless oil. MS (ES): m/z 518 [M+H]+.

Provenance & Evidence