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

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.

1. temperatureThe reaction mixture was heated at 95°-100° C. for 1.5 hours
2. temperaturecooled
3. extractionextracted with toluene (3x)
4. washThe combined organic extracts were washed with saturated sodium chloride solution (2 ×30 mL)
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. customevaporated
8. temperatureThe residual oil was heated with 6N hydrochloric acid (36 mL) for 3 hours
9. temperaturecooled
10. extractionextracted with methylene chloride
11. dry with materialThe combined organic extracts were dried over magnesium sulfate
12. customevaporated
13. filtrationThe cream-colored crystalline hydrochloride salt was filtered
14. customdried

ORD record

ord-8aab07cc7dad4fb2b3690f8d873e9752

Source dataset

uspto-grants-1997_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05631401