Toluene → HCID 67155338, compound

Participants

Reaction Steps

In a 100-mL flask a solution of 4-bromoaniline (20 g, 116 mmol) and ethyl-4,4,4-trifluoroacetoacetate (25.5 mL, 175 mmol, 1.5 equiv) in toluene (5 mL) is heated to reflux for 5 h, cooled and excess solvent removed to provide N-(4-bromophenyl)-4,4,4-trifluoroacetoacetamide (Structure 15 of Scheme XX). The crude reaction mixture is then dissolved in CH2Cl2 (40 mL) and water (10 mL) and then treated with N-fluorobenzenesulfonimide (1.1 equiv) at room temperature overnight. The reaction mixture is then diluted with water (30 mL) and partitioned. The aqueous layer is extracted with CH2Cl2 (3×75 mL), the combined organic layers are then washed with sat NaHCO3 (25 mL), saturated NH4Cl (2×25 mL), water (25 mL), Brine (25 mL), dried (MgSO4), filtered and concentrated to afford N-(4-bromophenyl)-2,4,4,4-tetrafluoroacetoacetamide (Structure 15a of Scheme XX). The crude product was then dissolved in concentrated H2SO4 (10 mL) and heated to 80° C. for 3-4 h, cooled to room temperature, and poured over NaOH pellets/ice. The cold aqueous solution was then filtered, the white precipitate was then redissolved in EtOAc (200 mL), washed with water (2×20 mL), Brine (25 mL), dried (MgSO4), filtered and concentrated to yield Compound 634 as a white powder: 1H NMR (400 MHz, DMSO-d6) 12.92 (bs, 1H), 7.83 (dd, J=8.0, 1.2, 1H), 7.77 (s, 1H), 7.41 (d, J=7.9, 1H).

Provenance & Evidence