1,2-Dichloroethane → HCID 57884061, compound

Participants

Reaction Steps

To a flask containing 2-iodo-4-trifluoromethylaniline (5.66 g, 19.7 mmol) were added pyruvic acid (4.17 mL, 59.2 mmol), DABCO (6.68 g, 59.2 mmol), magnesium sulfate (3.56 g, 29.6 mmol), and palladium acetate (443 mg, 1.97 mmol). The mixture was purged with N2 and dry DMF (60 mL) was added. The resultant suspension was deoxygenated via N2-sparge for 15 min, then was capped and placed in a 105° C. bath. After 48 h, the mixture was allowed to cool to room temperature. The insoluble materials were filtered and the filtrate was diluted with EtOAc. The organic phase was washed (H2O, then 1 N HCl), dried over anhydrous Na2SO4, and concentrated in vacuo: LCMS E, tr=2.95 min, m/z 228.1 [M−H]. To a flask containing the crude product obtained above were added EDC (8.0 g, 42.0 mmol), HOBt (5.67 g, 42.0 mmol) and N,O-dimethylhydroxylamine hydrochloride (4.10 g, 42.0 mmol). The resultant mixture was dissolved in DMF (30 mL), DIEA (11.8 mL, 67 mmol) was added, and the reaction mixture was stirred at 50° C. for 18 h. The mixture was then allowed to cool to room temperature and was quenched by pouring into sat. aq. NaHCO3. The aqueous phase was extracted with EtOAc (2×) and the combined organic phases were concentrated in vacuo. Purification by flash chromatography on silica gel (20 to 40%, then 40 to 100% EtOAc in hexanes) provided the title compound: LCMS B, tr=2.08 min, m/z 273.1 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 9.67 (br s, 1H), 8.02 (s, 1H), 7.52 (d, J=1.0 Hz, 2H), 7.31 (d, J=2.0 Hz, 1H), 3.86 (s, 3H), 3.46 (s, 3H).

Provenance & Evidence