Benzene, 1-bromo-4-(trifluoromethyl)- → HCID 71712048, compound

Participants

Reaction Steps

A vial was charged with N-(4-methoxybenzyl)-3-phenyl-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIATE R, 93.6 mg, 0.189 mmol), xantphos (21.89 mg, 0.038 mmol), Pd2(dba)3 (17.32 mg, 0.019 mmol), toluene (1891 μL), 1-bromo-4-(trifluoromethyl)benzene (31.8 μl, 0.227 mmol), and sodium tert-butoxide (36.4 mg, 0.378 mmol). The vial was sealed and placed in a 130° C. heating bath for 10 min. The reaction mixture was cooled to room temperature, diluted with water, and extracted with EtOAc (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was dissolved in DCM (0.5 mL) and TFA (0.5 mL). The resulting mixture was stirred for 20 minutes, then concentrated. The product was purified by chromatography on silica gel (0 to 5% MeOH/DCM) to give a yellow foam. The material was dissolved in MeOH/DCM and loaded onto a 1 g anion exchange column. The column was eluted with MeOH, then with 10% HCl/MeOH (prepared by dissolving 1 mL of conc. HCl in 9 mL of MeOH). The acidic fractions were concentrated, and the residue was concentrated from DCM to give 3-phenyl-N-(1,2,4-thiadiazol-5-yl)-4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (52.2 mg, 0.101 mmol) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.44 (s, 1 H), 7.71 (d, J=8.8 Hz, 2 H), 7.44 (d, J=8.4 Hz, 2 H), 7.37-7.23 (m, 6H), 7.16 (dd, J=3.3, 5.4 Hz, 2 H), 5.28-5.23 (m, 1 H), 4.60 (dd, J=2.4, 11.2 Hz, 1 H), 4.40 (dd, J=2.8, 11.3 Hz, 1 H). m/z (ESI) 519.0 (M+H)+.

Provenance & Evidence