Acetyl chloride → HCID 68432108, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 16.0 g (41.4 mmol) of 1-4 in 150 mL of pyridine was added 3.0 mL (62.1 mmol) of hydrazine hydrate, and the resulting mixture was heated at 90° C. for 45 min. After cooling to room temperature, the reaction was placed in an ice bath and 14.7 mL (207 mmol) of acetyl chloride was added dropwise. The bath was removed and the reaction was stirred overnight at room temperature before being dumped into a separatory funnel containing EtOAc and brine. The layers were separated, the organic was washed twice with 1M HCl, once with brine, dried over Na2SO4, and concentrated by rotary evaporation. The residue was twice resuspended in toluene and concentrated to azeotrope off any remaining pyridine. The residue was dissolved in 200 mL of MeOH and 8.0 g (42 mmol) of p-toluenesulfonic acid monohydrate was added. After stirring for 2 h at room temperature, most of the solvent was removed by rotary evaporation and the residue partitioned between saturated aqueous NaHCO3 and EtOAc. After separating the layers, the organic was washed again with bicarbonate, then brine, dried over Na2SO4, and concentrated by rotary evaporation. The residue was triturated with Et2O and the solid material was collected by filtration to provide racemic 1-5 as a white solid. Data for racemic 1-5: 1HNMR (500 MHz, CDCl3) δ 7.7 (m, 1H), 7.4-7.0 (m, 7H), 3.8-3.65 (m, 2H), 3.6 (m, 1H), 3.5 (m, 1H), 2.9 (m, 1H), 2.4 (s, 3H), 2.3 (m, 1H), 1.7-1.5 (m, 2H) ppm. HRMS (ES) calc'd M+H for C20H20F2N2O3: 359.1566. Found: 359.1557

Provenance & Evidence