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

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, 6-bromo-N-methyl-2-naphthamide (10.0 g, 37.9 mmol) was added to tetrahydrofuran (250 mL), and to the obtained solution was added dropwise 2.0 mol/L isopropylmagnesium chloride tetrahydrofuran solution (18.9 mL) at room temperature. The obtained reaction mixture was cooled to −30° C., 1.65 mol/L n-butyllithium hexane solution (37.9 mL) was added dropwise thereto, and the mixture was stirred at the same temperature for 1 hr or more. To the obtained reaction mixture was added dropwise a solution of 1-tosyl-4-formyl-1H-imidazole (14.2 g, 56.8 mmol) in tetrahydrofuran (200 mL) at −20° C., and the mixture was stirred at the same temperature for 2 hr. The obtained reaction mixture was warmed over 2 hr to 0° C., 20 w/v % aqueous ammonium chloride solution (150 mL) was added dropwise thereto. The separated organic layer was concentrated to the volume of about 130 mL under reduced pressure to give a residue. To the obtained residue was added tetrahydrofuran (200 mL), and the mixture was concentrated to the volume of about 130 mL under reduced pressure to give a residue. To the obtained residue was added acetone (200 mL), and the mixture was concentrated to the volume of about 200 mL under reduced pressure. These operations were repeated three times to give a residue. To the obtained residue was added acetone to adjust the volume to about 260 mL. The obtained solution was stirred at room temperature for 2 hr or more. The obtained crystals were collected by filtration, and washed with acetone (100 mL) to give wet crystals. The obtained wet crystals were dried under reduced pressure at an outside temperature of 50° C. to give 6-(hydroxy(1-tosyl-1H-imidazol-4-yl)methyl)-N-methyl-2-naphthamide (8.5 g, 19.5 mmol). yield 52%.

Provenance & Evidence