Benzoyl chloride → HCID 20610787, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of nucleoside 64 (232.7 mg, 0.66 mmol) in anhydrous acetonitrile (3 cm3) was added a solution of 1,2,4-triazole (420 mg, 6.1 mmol) and POCl3 (0.12 cm3, 1.3 mmol) in anhydrous acetonitrile (5 cm3). The reaction mixture was cooled to 0° C. and anhydrous triethylamine (0.83 cm3) was added, whereupon the mixture was kept for 90 min at room temperature. Triethylamine (0.54 cm3) and water (0.14 cm3) was added, and the reaction mixture was stirred for 10 min and evaporated under reduced pressure. The residue was dissolved in EtOAc and washed with a saturated aqueous solution of sodium hydrogencarbonate (2×9 cm3) and water (9 cm3). The aqueous phase was extracted with dichloromethane (3×20 cm3). The combined organic phase was evaporated under reduced pressure and the residue was redissolved in dioxane (4 cm3), whereupon 32% aqueous ammonia (0.7 cm3) was added. After stirring for 3 h, the reaction mixture was evaporated under reduced pressure and coevaporated with anhydrous pyridine. The residue was dissolved in anhydrous pyridine (3.6 cm3) and benzoyl chloride (0.42 cm3, 3.6 mmol) was added. After stirring for 2 h, the reaction was quenched with water (1 cm3) and the reaction mixture was evaporated under reduced pressure. The residue was then redissolved in EtOAc and washed with water (3×7 cm3). The organic phase was evaporated to dryness under reduced pressure, and the residue was dissolved in pyridine/methanol/water (13:6:1, v/v/v, 14 cm3) at 0° C., and a 2M solution of NaOH in pyridine/methanol/water (13:6:1, v/v/v, 7 cm3) was added. After stirring for 20 min, the reaction mixture was neutralised using a 2M solution of HCl in dioxane, and the reaction mixture was evaporated under reduced pressure. The residue was purified by silica column chromatography using dichloromethane/methanol (95:5, v/v) as eluent to give nucleoside 65 as a yellow foam (94.6 mg, 38%). δH (CD3OD) 8.21 (1H, br, s), 8.02 (1H, m), 7.84-7.9 (1H, m), 7.41-7.58 (4H, m), 5.61 (1H, s), 4.36 (1H, s), 4.10 (1H, s), 3.98 (1H, d, J 8.0), 3.94 (2H, s), 3.78 (1H, d, J 7.9), 2.11 (3H, d, J 1.0). δC (CD3OD, selected signals) 133.66, 132.90, 130.63, 129.50, 129.28, 128.65, 90.71, 88.86, 80.57, 72.47, 70.22, 57.53, 14.01. FAB-MS m/z 374 [M+H]+.

Provenance & Evidence