Potassium Phosphate, Dibasic → 3-(4-Chlorophenyl)-5-(trifluoromethyl)-1H-pyrrole-2-carboxylic acid

Participants

Reaction Steps

In 6 separate tubes, 3-(4-chlorophenyl)-1H-pyrrole-2-carboxylic acid (1 g, 4.51 mmol) and K2HPO4 (2.36 g, 13.54 mmol) were combined in dry MeCN (40 mL) and degassed with Ar for 10 min. Dichlorotris(1,10-phenanthroline)ruthenium(II) hydrate (0.130 g, 0.180 mmol) was added, followed by trifluoromethanesulfonyl chloride (0.53 mL, 4.96 mmol) and the suspension was irradiated with a fluorescent light bulb (E27-32W, 4000K, 65 mA) at 40° C. for 20 h. More trifluoromethanesulfonyl chloride (0.24 mL, 2.250 mmol) was added and the irradiation was continued for 24 h. More trifluoromethanesulfonyl chloride (0.24 mL, 2.250 mmol) was added and the irradiation was continued for 48 h. More trifluoromethanesulfonyl chloride (0.24 mL, 2.250 mmol) was added and the irradiation was continued for 72 h. More degassed dry MeCN (5-10 mL per vial) was added to fill up the vials and more trifluoromethanesulfonyl chloride (0.5 mL, 4.69 mmol) was added. The irradiation was continued for 20 h. More trifluoromethanesulfonyl chloride (0.5 mL, 4.69 mmol) was added and the irradiation was continued for 24 h. The reaction mixtures were combined and filtered over a short plug of silica (eluent EtOAc). The filtrate was concentrated in vacuo and stirred with i-Pr2O (100 mL) to give a brown suspension. The solids were filtered off and the filtrate was concentrated in vacuo. The residue was absorbed on hydromatrix and purified using column chromatography (silica, gradient heptane/EtOAc 2:1−>1:2) to give a brown oil which solidified upon standing. The solid was treated with MeCN (5 mL), filtered off and washed with MeCN (3×5 mL) to give the desired product (1.37 g, 17%) as a white solid. The mother liquor was concentrated in vacuo and the residue was triturated with DCM to give the starting material (156 mg, 2%) as a light yellow solid. The mother liquor (4.9 g) was absorbed on hydromatrix and purified using column chromatography (silica, gradient heptane/EtOAc 7:3−>2:3) to give impure fractions which were combined and crystallised from MeCN. The product was filtered off and washed with a mixture of heptane and MeCN (˜1:1, 2×3 mL) and dried to give another batch of the desired product (468 mg, 6%) as a white solid. The mother liquor was concentrated in vacuo to give the desired product (1.23 g, 78% pure) as a brown oil. From the column more impure product was retrieved to give the title compound (1.86 g, 51% pure) as a brown oil.

Provenance & Evidence