Indole → 5-Methoxy-2-methyl-1H-indole-3-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

Phosphorous oxychloride (12.7 ml, 0.136 mol) is added dropwise at 0° C. to dimethylformamide (42.4 ml, 0.544 mol) over 30 minutes. A solution of 5-methoxy-2-methylindole (20 g, 0.124 mol) in 40 ml of DMF is added dropwise over 45 minutes. When 30 ml of the indole solution has been added, it becomes necessary to add 10 ml of DMF to break up the heavy paste which forms. The reaction mixture is then warmed to 35° C. for one hour. After 30 minutes the reaction again becomes too pasty, and 5 ml more of DMF is added. The bath is removed, and 60 g of crushed ice is added quickly to the reaction mixture. The reaction mixture is stirred for 30 minutes followed by addition of 20 ml of water and 40 g of ice. A solution of sodium hydroxide (25 g) in water (200 ml) is added dropwise to the red solution. After the first one-third of this sodium hydroxide solution has been added, the color changes to yellow, and the remainder of the sodium hydroxide solution is added quickly. It is rapidly brought to a boil (100°-120° C.) for 10 minutes, cooled and refrigerated overnight. The solid is filtered and washed four times with cool water. It is dried in a vacuum oven at 50° C. for 22 hours to give 23.0 g (98%) of powdery yellow crystals of pure 5-methoxy-2-methyl-1H-indole-3-carboxaldehyde; mp 190°-191° C.

Provenance & Evidence