Carbon Dioxide → HCID 57835218, compound

Participants

Reaction Conditions

Reaction Steps

A dry 25 mL 3-neck RBF, fitted with a magnetic stirring bar, a thermometer and septum with Ar inlet was charged with 5-bromo-2-methoxy-4-methylbenzene-sulfonamide 12e (0.586 g, 2.1 mmol), anhydrous THF (5 mL) and HMPA (0.37 mL, 2.1 mmol). The mixture was cooled to −75° C. and a 2.0 M solution of LDA (4.2 mL, 8.4 mmol) was added drop wise via a syringe. The reaction mixture was stirred at −75° C. for 1.5 hours and then cannulated into a flask containing 20 g of dry ice and 5 mL THF and left to warm up slowly to RT. The solvent was removed under reduced pressure and H2O (20 mL) was added to the residue. At this point, some of the unreacted starting material precipitated and was removed by filtration. The filtrate was acidified and the solution was extracted with EtOAc (3×20 mL). The combined organic layers were evaporated to dryness, the residue was treated with an aqueous solution of saturated NaHCO3 (10 mL) and the insoluble material was separated by filtration. The filtrate was acidified with concentrated HCl and the cloudy solution extracted again with EtOAc (3×5 mL). The combined organic layers were concentrated to ˜1 mL, causing crystallization of the product, which was collected by filtration to give pure (2-bromo-5-methoxy-4-sulfamoylphenyl)acetic acid (20 mg) 12f (˜3% yield).

Provenance & Evidence