Benzophenone imine → 4-(4-methoxybenzylthio)-N-(diphenylmethylene)pyridine-2-amine

Participants

Reaction Conditions

Reaction Steps

4-(4-methoxybenzylthio)-2-chloropyridine (12 g, 45.2 mmol) and diphenylmethanimine (8.7 ml, 52.0 mmol) were dissolved in toluene (300 mL). The solution was evacuated and purged with nitrogen. Pd(OAc)2 (0.51 g, 2.3 mmol), rac-Binap (1.41 g, 2.26 mmol), and NaOtBu (6.1 g, 63.2 mmol) were added. The mixture stirred under N2 at 100° C. for 90 minutes. After cooling to ambient temperature, the mixture was quenched with water and the material was extracted with EtOAc, dried, and concentrated to afford the 4-(4-methoxybenzylthio)-N-(diphenylmethylene)pyridine-2-amine crude intermediate (18.5 g). The crude imine was dissolved in MeOH (200 mL) and hydroxylamine hydrochloride (11.0 g, 158 mmol) and sodium acetate trihydrate (30.7 g, 226 mmol) were added. The reaction was stirred at ambient temperature for 2 hours, then diluted with 1N HCl and extracted with EtOAc. The aqueous layer was basified to pH 9 and extracted with EtOAc. This second EtOAc layer was dried and concentrated to provide 4.7 g of the desired product. An additional 4.3 g of product was isolated by concentrating the first EtOAc layer extraction and purified via flash chromatography (70% EtOAc/hexanes) to provide the desired product (Total yield: 9.0 g, 80%) was isolated as a yellow solid.

Provenance & Evidence