Aminoacetaldehyde dimethyl acetal → 6-Methoxy-7-methylisoquinoline

Temperature

-10 °C

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%).

1. customto prepare a solution
2. temperaturethe mixture was heated
3. temperatureunder reflux overnight
4. customThe solvent was removed by distillation under the reduced pressure
5. dissolutionthe residue was then dissolved in tetrahydrofuran (30 ml)
6. additionEthyl chloroformate (2.17 g) and trimethyl phosphite (2.97 g) were added
7. customThe solvent was removed by distillation under the reduced pressure
8. dissolutionthe residue was then dissolved in dichloromethane (30 ml)
9. additiontitanium tetrachloride (22.7 g) was added to the solution
10. temperaturethe mixture was heated
11. temperatureunder reflux for 36 hr
12. temperatureThe reaction solution was cooled to room temperature
13. extractionwas extracted with 3 N hydrochloric acid
14. additionThe aqueous layer was made basic by the addition of a 3 N aqueous sodium hydroxide solution
15. extractionwas then extracted with dichloromethane
16. customThe solvent was removed by distillation under the reduced pressure

ORD record

ord-8f1ea0b70d5d4e14ae7d2430c5424f85

Source dataset

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07560558B2