Ammonium Chloride → [1-(2,4-Dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]methanol

Participants

Reaction Conditions

Reaction Steps

To a suspension of methyl 1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate (15.0 g, 39.9 mmol) was added lithium aluminum hydride (3.03 g, 79.8 mmol) at 0° C., and the mixture was stirred at 0° C. for 30 min. The mixture was poured into crashed ice, neutralized with aqueous saturated ammonium chloride, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give the crude product of [1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]methanol (13.7 g). To a solution of the above crude product in triethylamine (43.6 mL), dimethylsulfoxide (200 mL), and dichloromethane (40 mL) was added sulfur trioxide-pyridine complex (43.8 g, 275 mmol), and the mixture was stirred at room temperature for 12 hr. The mixture was diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 15-60% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was washed with diisopropyl ether to give the title compound as a pale yellow powder (11.6 g, 33.5 mmol, 84% in 2 steps).

Provenance & Evidence