Dimethylformamide → 5-[2-{[(Tert-butoxycarbonyl)amino]methyl}-4-(dimethylamino)phenyl]thiophene-2-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A solution of tert tert-butyl (2-bromo-5-methoxybenzyl)carbamate (0.226 g, 0.69 mmol), 5-(dihydroxyboryl)thiophene-2-carboxylic acid (0.118 g, 0.69 mmol) and cesium carbonate (0.492 g, 1.51 mmol) in DMF (2 mL) and water (1 mL) was degassed. To this solution was added PdCl2dppf (1:1 complex with DCM, 0.020 g, 0.03 mmol). The reaction mixture was heated at 100° C. for 36 hr and then allowed to cool to rt and concentrated. The residue was suspended in acetonitrile (15 mL) and MeOH (2 mL) containing 0.1% TFA and adsorbed onto celite and purified by reverse phase chromatography to give a mixture of the desired product and remaining starting material. This mixture was suspended in half-saturated sodium bicarbonate solution (10 mL) and washed with EtOAc (20 mL). The organic solution was extracted with half-saturated sodium bicarbonate solution until no product was apparent in the organic solution. The pH of the aqueous solution was adjusted to 5 with 1N HCl and then was extracted with EtOAc. The organic solutions were combined, washed with brine, dried over Na2SO4, filtered and concentrated to give 5-[2-{[(tert-butoxycarbonyl)amino]methyl}-4-(dimethylamino)phenyl]thiophene-2-carboxylic acid (0.036 g, 13%) as a yellow oil. LCMS: (AA) ES+ 377.2, ES-375.3.

Provenance & Evidence