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

Participants

Reaction Steps

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%).

Provenance & Evidence