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

Participants

Reaction Steps

A mixture of m-methoxyphenethylamine (25 g, 0.165 mol), 37% formaldehyde (12.7 mL) and water (12.7 mL) was stirred for 20 minutes. The reaction mixture was heated at 95°-100° C. for 1.5 hours, cooled, diluted with ice-water, and extracted with toluene (3x). The combined organic extracts were washed with saturated sodium chloride solution (2 ×30 mL), dried over magnesium sulfate, filtered and evaporated. The residual oil was heated with 6N hydrochloric acid (36 mL) for 3 hours, cooled, basified with 50% aqueous sodium hydroxide solution and extracted with methylene chloride. The combined organic extracts were dried over magnesium sulfate and evaporated; the residue was converted to its hydrochloride salt with HCl (g) in isopropanol. The cream-colored crystalline hydrochloride salt was filtered and dried affording the title compound in 52% yield. m.p. 232°-234° C.

Provenance & Evidence