Benzene, 1-bromo-2-(trifluoromethyl)- → 6-(hydroxy(1-trityl-1H-imidazol-4-yl)methyl)-N-methyl-2-naphthamide

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, o-bromotrifluoromethylbenzene (1.35 kg, 6.00 mol) was added to tetrahydrofuran (7.9 L). The reaction mixture was cooled to −70° C., 1.6 mol/L n-butyllithium hexane solution (3.75 L, 6.00 mol) was added dropwise thereto, and the mixture was stirred at the same temperature for about 30 min. The reaction mixture was added dropwise at the same temperature to a solution prepared by adding 6-bromo-N-methyl-2-naphthamide (1.13 kg, 4.28 mol) to THF (62.2 L) at −70° C. under a nitrogen atmosphere, and the mixture was stirred for 1.5 hr. To the reaction mixture were added dropwise successively 1.6 mol/L n-butyllithium hexane solution (2.67 L, 4.27 mol) and a solution of 1-trityl-4-formyl-1H-imidazole (1.21 kg, 3.58 mol) in THF (7.9 L) at the same temperature, and the mixture was stirred for 2 hr. The reaction mixture was allowed to warm to −10° C., and 20 w/v % aqueous ammonium chloride solution (17.0 L) was added dropwise thereto at −10 to 0° C. The separated organic layer was concentrated under reduced pressure. To the residue was added ethyl acetate (11.3 L), and the mixture was stirred at room temperature. The crystals were collected by filtration, and washed with ethyl acetate (11.3 L). The obtained wet crystals were dried under reduced pressure to give 6-[hydroxy(1-trityl-1H-imidazol-4-yl)methyl]-N-methyl-2-naphthamide (1.31 kg, 2.50 mol). yield 58%.

Provenance & Evidence