Hydrochloric Acid → HCID 17981723, compound

Participants

Reaction Conditions

Reaction Steps

Charge a 5 L round bottom flask equipped with dry ice/acetone bath, nitrogen atmosphere, mechanical stirrer, thermocouple, and addition funnel with septum with 1-isopropylsulfonyl-2-amino-6-iodobenzimidazole (125 g, 342 mmol) and tetrahydrofuran (1.2 L) and cool to −77° C. (results in a slurry). To this slurry add phenyllithium (1.8 M in cyclohexane/diethyl ether, 599 mL, 1078 mmol) over 25 minutes keeping the temperature below −67° C. After stirring the resulting green slurry for 20 minutes while cooling to −77° C., add tert-butyllithium (1.7 M in pentane, 503 mL, 856 mmol) over 25 minutes keeping the temperature of the reaction below −67° C. Stir the mixture at −75° C. for 40 minutes then add triisopropyl borate (276 mL, 1198 mmol) over 15 minutes keeping the temperature below −65° C. Warm the resulting slurry slowly to 0° C. over 2 hours, then add a mixture of concentrated hydrochloric acid and water (400 mL) until pH 2 is reached. Stir the mixture for 1 hour then adjust to pH>12 with 5 N sodium hydroxide while keeping the temperature <10° C. Add water (1 L), and separate the layers. Wash the aqueous layer with ethyl acetate (300 mL) then adjust to pH 6 with concentrated hydrochloric acid. Extract the mixture with ethyl acetate (2×700 mL), dry the combined extracts over sodium sulfate, filter, and concentrate in vacuo to an orange paste (116 g). Dissolve the paste in warm (˜60° C.) 2-propanol (360 mL) then add water (1.4 L). Cool the solution to 0° C. for 3 hours. Collect the resulting solid by filtration, wash with water then air-dry to constant weight to afford the title compound (34.9 g, 36% yield) as light tan crystals. Obtain a second crop from the filtrate (4.95 g, 41% yield overall). MS (ES+): m/z=284 (M+H)+

Provenance & Evidence