Hydrochloric Acid → HCID 58092306, compound

Participants

Reaction Steps

To a solution of ethyl 2-pyridylacetate (9.2 mL, 60.5 mmol) in EtOH (100 mL) were added 6 N HCl (16 mL) and PtO2 (1 g). The reaction was stirred at room temperature under H2 until complete. After the solvent was removed, the residue was diluted with 2 M NH4OH solution until the solution was slightly basic. The mixture was extracted with ether (3×50 mL), and the combined organics were dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting yellow oil was diluted with EtOH (100 mL), and ethyl acrylate (14.5 mL, 133 mmol) and TEA (36.0 mL, 256 mmol) were added. The reaction mixture was stirred at room temperature under argon for three days. The mixture was concentrated, and the resulting colorless oil was dried under vacuum. The oil was dissolved in THF (25 mL) and cooled to −78° C. LiHMDS (84 mL, 84 mmol) was added in dropwise, and the mixture was stirred at −78° C. for 2 h. The reaction was quenched with H2O, diluted with ether, washed with sat. NaHCO3 solution and dried over Na2SO4. The organic solution was filtered and concentrated. The resulting oil was diluted with 6 M HCl (70 mL) and heated to reflux overnight. After cooling, the reaction mixture was neutralized with solid KHCO3, extracted with ether and dried over Na2SO4. The organic solution was filtered and concentrated. The resulting oil was dissolved in EtOH (15 mL), and 1-(3-bromophenyl)-1-methylhydrazine hydrochloride (2.1 g, 8.81 mmol) was added followed by concentrated HCl (15 mL). The reaction mixture was heated to reflux overnight. The mixture was concentrated, and the residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2) to give the title compound (0.25 g, 10%) as an off-white solid: 1H NMR (500 MHz, CDCl3) δ 7.48 (d, J=1.5 Hz, 1H), 7.42 (d, J=8.5 Hz, 1H), 7.08 (dd, J=8.5, 1.5 Hz, 1H), 3.60 (s, 3H), 3.44-3.41 (m, 1H), 3.15-3.11 (m, 1H), 3.05-3.01 (m, 2H), 2.79-2.74 (m, 1H), 2.72-2.67 (m, 1H), 2.64-2.61 (m, 1H), 2.57-2.51 (m, 1H), 1.92-1.89 (m, 1H), 1.79-1.73 (m, 2H), 1.63-1.50 (m, 2H); ESI MS m/z 319 [M+H]+.

Provenance & Evidence