Sodium Hydroxide → 6-(1-Benzyl-3-pentyl-1H-indol-2-yl)-2-naphthol

Participants

Reaction Conditions

Reaction Steps

1-benzyl-2-(6-methoxynaphthalen-2-yl)-3-pentyl-1H-indole (210.0 g, 0.484 mol) was dissolved in methylene chloride (620 mL), the solution was cooled to 0° C., and 1.0 M boron tribromide in methylene chloride (363 mL, 0.363 mole) was added to the solution over 30 minutes. The reaction mixture was stirred for twelve hours at 20° C. to 25° C., at which point in time HPLC analysis indicated that no starting material was present. The solution was cooled to 0° C.-10° C. and a 5% aqueous sodium hydroxide solution (462 mL, 0.605 mole) was added to the solution over 30 minutes. The mixture was stirred for 30 minutes and the layers were separated. The organic layer was washed with 15% aqueous sodium chloride (170 mL) and passed through a silica gel pad (210 g). The pad was washed with two 250 mL portions of methylene chloride. The combined filtrate was concentrated by atmospheric distillation to a volume of 500 mL, toluene (260 mL) was added, and distillation was resumed until the volume reached 500 mL. The temperature increased to 75° C.-80° C. during the distillation. Heptane (1040 mL) was then added while maintaining the temperature. The mixture was cooled to 55° C. over 50 min. Approximately 10 grams of the solution were withdrawn from the reactor, subjected to low-temperature crystallization, and returned to the solution as a seeding suspension at 55° C. Crystallization began at 43° C.-45° C. The suspension was cooled to 0° C.-5° C. and stirred at that temperature for two hours. The solid was filtered, washed with 500 mL heptane, and dried at 50° C./50 torr for 24 hours to produce 166.0 g (81.7% yield) of the title compound as an off-white solid with 99.89% ar. HPLC purity.

Provenance & Evidence