Formaldehyde → 6-Methoxy-4,4-dimethyl-1,2,3,4-tetrahydroisoquinoline

A mixture of 2-(3-methoxyphenyl)-2-methylpropylamine (7.5 g, 0.042 mol), 40% aqueous formaldehyde (3.2 g, 0.043 mol) and water (3.2 ml) was stirred at room temperature for 3 hours then heated on a steam bath for 0.5 hour. On cooling the mixture was partitioned between water (100 ml) and dichloromethane (50 ml) and the aqueous layer extracted with dichloromethane (3×50 ml). Combined extracts were dried (Na2SO4) and evaporated in vacuo. The residue was mixed with water (3.6 ml) and concentrated hydrochloric acid (5 ml) and heated on a steam bath under argon for 2 hours. On cooling, water (300 ml) was added and the mixture washed with dichloromethane (2×50 ml). The aqueous layer was basified with solid potassium carbonate and extracted into dichloromethane (3×75 ml). Combined extracts were dried (Na2SO4) and evaporated in vacuo to afford the title compound as a pale yellow oil (6.5 g, 85%).

1. temperaturethen heated on a steam bath for 0.5 hour
2. temperatureOn cooling the mixture
3. customwas partitioned between water (100 ml) and dichloromethane (50 ml)
4. extractionthe aqueous layer extracted with dichloromethane (3×50 ml)
5. dry with materialCombined extracts were dried (Na2SO4)
6. customevaporated in vacuo
7. additionThe residue was mixed with water (3.6 ml) and concentrated hydrochloric acid (5 ml)
8. temperatureheated on a steam bath under argon for 2 hours
9. temperatureOn cooling
10. additionwater (300 ml) was added
11. washthe mixture washed with dichloromethane (2×50 ml)
12. extractionextracted into dichloromethane (3×75 ml)
13. dry with materialCombined extracts were dried (Na2SO4)
14. customevaporated in vacuo

ORD record

ord-687703a435864994b3fa1560ff566a99

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06358974B1