Ammonium Chloride → 6-(hydroxy(1-trityl-1H-imidazol-4-yl)methyl)-N-methyl-2-naphthamide

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, 6-bromo-N-methyl-2-naphthamide (7.0 g, 26.5 mmol) was added to tetrahydrofuran (175 mL), and then 2.0 mol/L isopropylmagnesium chloride tetrahydrofuran solution (13.7 mL) was added dropwise thereto at room temperature. The reaction mixture was cooled to −30° C., 1.6 mol/L n-butyllithium hexane solution (26.6 mL) was added dropwise thereto, and the mixture was stirred at the same temperature for 2 hr. To the reaction mixture was added dropwise a solution of 1-trityl-4-formyl-1H-imidazole (13.5 g, 39.9 mmol) in tetrahydrofuran (140 mL) at −20° C., and the mixture was stirred at the same temperature for 2 hr. The reaction mixture was allowed to warm to 0° C., and stirred for 1 hr, and 20 w/v % aqueous ammonium chloride solution (105 mL) was added dropwise thereto. The organic layer was separated, and concentrated to the volume of about 90 mL under reduced pressure. To the residue was added tetrahydrofuran (140 mL), and the mixture was concentrated to the volume of about 90 mL under reduced pressure. To the residue was added acetone (140 mL), and the mixture was concentrated to the volume of about 140 mL under reduced pressure. These operations were repeated three times. To the residue was added acetone to adjust the volume to about 180 mL, and the mixture was stirred at room temperature. The crystals were collected by filtration, and washed with acetone (70 mL). The obtained wet crystals were dried under reduced pressure to give 6-[hydroxy(1-trityl-1H-imidazol-4-yl)methyl]-N-methyl-2-naphthamide (10.3 g, 19.7 mmol). yield 74%.

Provenance & Evidence