4-Nitrobenzoyl chloride → HCID 87628157, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of the compound of Example 13A (34 g, 92 wt %, 77 mmol) and NaHCO3 (3.3 g, 39 mmol) in 300 mL dichloromethane and 60 mL methanol was cooled to ←70° C. and treated with ozone (7-8 psi, 90 volts, 4 slpm) until a persistent blue color was observed. After purging with nitrogen to remove the color, the reaction was warmed to ˜0° C., then filtered through paper and concentrated. After chasing with 2×100 mL benzene, 300 mL of dichloromethane and 60 mL of pyridine were added and the reaction was cooled to <5° C. p-Nitrobenzoyl chloride (22.2 g, 120 mmol) was added and stirred for 1 hour, then the bath was removed and the reaction stirred at ambient temperature overnight. The resulting suspension was concentrated in vacuo to a thick slurry, and then diluted with ethyl acetate, and the solids were removed by filtration. The filtrate was washed with 250 mL of saturated aqueous sodium bicarbonate, then with 100 mL each of 2 N HCl, 1 N HCl, and 2 N HCl, and with 200 mL each of 1 N HCl, saturated aqueous sodium bicarbonate, and brine. The organic layer was dried over MgSO4, filtered and concentrated to yield the crude ester. A sample of this product (20.6 g, 32 mmol) was dissolved in 115 mL methanol; 15 mL water was added, followed by 11.0 g of K2CO3. After 2 hours, the reaction was quenched with 6.5 mL of acetic acid, and then concentrated in vacuo. The residue was treated with 100 mL water, and then extracted sequentially with 150 mL and 100 mL of ethyl acetate. The combined organic layers were washed with 100 mL each of saturated aqueous sodium bicarbonate, then 10% aqueous NaCl, then 20% aqueous NaCl. The ethyl acetate layer was dried over MgSO4, filtered and concentrated. Chromatography (Isco CombiFlash® system, Analogix RS 300 300 g column, 1:9 ethyl acetate: dichloromethane for 5 minutes, then to 12:88 over 35 minutes, then hold for 10 minutes) provided the title compound (10.3 g, 91 wt %, 76%).

Provenance & Evidence