Aminoacetaldehyde dimethyl acetal → 8-(Trifluoromethyl)isoquinoline

A mixture of 2-trifluoromethylbenzaldehyde (15 g; 86 mmol) and aminoacetaldehyde dimethylacetal (9.37 ml; 86 mmol) in toluene (75 ml) was heated at reflux under Dean/Stark conditions for 2 hours. The cooled reaction mixture was evaporated to dryness and the residue added dropwise to conc. sulfuric acid (200 ml) at 140° C.; after complete addition the heating was continued for 30 mins then the warm mixture was poured over ice. The mixture was filtered and the filtrate basified by the addition of 4N NaOH with cooling. The basic solution was extracted with Et2O (×3), the combined Et2O layers were dried over Na2SO4, filtered and evaporated. The residue was dissolved in DCM and filtered through a short plug of silica and evaporated to give 1.2 g (Yield 7%).

1. temperaturewas heated
2. temperatureat reflux under Dean/Stark conditions for 2 hours
3. customThe cooled reaction mixture
4. customwas evaporated to dryness
5. additionthe residue added dropwise to conc. sulfuric acid (200 ml) at 140° C.
6. additionafter complete addition the heating
7. additionthe warm mixture was poured over ice
8. filtrationThe mixture was filtered
9. additionthe filtrate basified by the addition of 4N NaOH
10. temperaturewith cooling
11. extractionThe basic solution was extracted with Et2O (×3)
12. dry with materialthe combined Et2O layers were dried over Na2SO4
13. filtrationfiltered
14. customevaporated
15. dissolutionThe residue was dissolved in DCM
16. filtrationfiltered through a short plug of silica
17. customevaporated
18. customto give 1.2 g (Yield 7%)

ORD record

ord-17405de67d2145878a399f5d2f9e9279

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07285563B2