Aminoacetaldehyde dimethyl acetal → 6-Methoxy-7-methylisoquinoline

Participants

Reaction Conditions

Reaction Steps

4-Methoxy-3-methylbenzaldehyde (3.00 g) was dissolved in benzene (30 ml) to prepare a solution. 2,2-Dimethoxy-ethylamine (2.10 g) was added to the solution, and the mixture was heated under reflux overnight. The solvent was removed by distillation under the reduced pressure, the residue was then dissolved in tetrahydrofuran (30 ml), and the mixture was cooled to −10° C. Ethyl chloroformate (2.17 g) and trimethyl phosphite (2.97 g) were added thereto, and mixture was stirred at room temperature overnight. The solvent was removed by distillation under the reduced pressure, the residue was then dissolved in dichloromethane (30 ml), titanium tetrachloride (22.7 g) was added to the solution, and the mixture was heated under reflux for 36 hr. The reaction solution was cooled to room temperature, was then neutralized with a 1 N aqueous sodium hydroxide solution, and was extracted with 3 N hydrochloric acid. The aqueous layer was made basic by the addition of a 3 N aqueous sodium hydroxide solution and was then extracted with dichloromethane. The solvent was removed by distillation under the reduced pressure to give 6-methoxy-7-methylisoquinoline (764 mg, yield 22%).

Provenance & Evidence