Dimethylformamide → 5h-[1,3]Dioxolo[4,5-f]indole-7-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

To an ice cold solution of DMF (50 mL, excess) was added POCl3 (8 mL, 85.7 mmol) in a drop wise fashion. After addition the mixture was stirred at 0° C. for 5 min and at room temperature for 45 min. The mixture was cooled to 0° C. and 5,6-methylenedioxy-indole (10 g, 62.1 mmol) was added in portion. After complete addition, the mixture was stirred at 0° C. for 10 min and at room temperature for 20 min and finally at 60° C. for 6 h. The mixture was cooled to room temperature and then to 0° C. followed by the addition of 1N NaOH solution (150 mL). The mixture was stirred at room temperature for 30 min as result a homogenous solution was obtained. To the mixture was added 100 mL of water and stirring was continued at room temperature overnight. The product, 5,6-methylenedioxy-indole-3-carboxaldehyde separated as a solid, which was filtered, washed (water followed by hexane) and dried. The filtrate also provided additional product upon extraction from ethyl acetate (3 times). The combined organic extractions were washed successively with water and brine. After drying over MgSO4, solvent was evaporated. A solid was obtained which was suspended in 100 mL of diethyl ether, sonicated for few minutes and was filtered. The solid was further washed with diethyl ether and was dried. A combined crude yield of 8.08 g (69%) of the 5,6-methylenedioxy-indole-3-carboxaldehyde was obtained which was subjected to N-methylation without further purifications. To a cold (0° C.) solution of 5,6-methylenedioxy-indole-3-carboxaldehyde (see above) (8 g, 42.32 mmol) in dry DMF (40 mL) was added NaH (60% dispersion in mineral oil, 2.1 g, 52.5 mmol). The resulting mixture was stirred at 0° C. for 30 min. Iodomethane (5 mL, 80.3 mmol) was added dropwise to the reaction mixture. The mixture was stirred at 0° C. for 15 min and at room temperature for 2 h. The mixture was cooled to 0° C. and was quenched with water. The mixture was further diluted with water (˜700 mL). The product, 5,6-methylenedioxy-1-methyl-indole-3-carboxaldehyde separated as a solid which was filtered, washed (water followed by hexane) and dried to provide 6.2 g (72% yield) of the desired product. MS: 204 (M+H).

Provenance & Evidence