Methanol → N-(2,4-dimethoxybenzyl)thiazol-2-amine

Participants

Reaction Steps

2,4-Dimethoxybenzaldehyde (25 g, 150 mmol), 2-aminothiazole (15.1 g, 150 mmol) and piperidine (150 mg, 1.76 mmol) were combined in dichloroethane (500 ml) and the mixture was heated to reflux over 4 Å molecular sieves for 18 hours. The sieves were removed by filtration and the reaction mixture diluted with methanol (300 ml). Sodium borohydride (25 g, 662 mmol) was added in portions and the reaction mixture heated to reflux for 2 hours. The cooled reaction mixture was quenched with water (50 mL) and the organic solvents evaporated in vacuo. The aqueous residue was extracted with ethyl acetate (2×100 mL) and the combined organic solutions extracted with 2M HCl (2×50 mL). The acidic solution was basified with solid potassium carbonate and re-extracted with ethyl acetate (2×50 mL). The organic layer was dried over Na2SO4, filtered and evaporated in vacuo. The residue was purified by column chromatography eluting with 9:1 dichloromethane:methanol to yield the title compound (24 g, 96 mmol, 64%).

Provenance & Evidence