Triethylamine → 8-Azido-5,6,7,8-tetrahydroquinoline

Temperature

40 °C

To a stirred solution of 8-hydroxy-5,6,7,8-tetrahydroquinoline (71.6 g, 0.480 mol) in CH2Cl2 (500 mL, 1.0 M) at room temperature was added triethylamine (126 mL, 0.904 mol) followed by methanesulfonyl chloride (55 mL, 0.711 mol). The resulting mixture was heated to 40° C. overnight then cooled to room temperature. The mixture was poured into water (350 mL), diluted with CH2Cl2 (350 mL), and the phases were separated. The organic phase was washed with brine (2×250 mL), dried (Na2SO4), and concentrated. The resultant oil was dissolved in DMF (570 mL), treated with sodium azide (63.1 g, 0.971 mol), and heated at 70° C. overnight. The mixture was cooled to room temperature, then evaporated and the residual slurry was poured into brine (500 mL) and extracted with ether (4×500 mL). The combined organic extracts were washed with brine (2×100 mL), dried (Na2SO4), and concentrated. The crude material was filtered through a short plug of silica gel (CH2Cl2) to provide 41.0 g (46% from 5,6,7,8-tetrahydroquinoline) of 8-azido-5,6,7,8-tetrahydroquinoline as a red oil.

1. temperaturethen cooled to room temperature
2. customthe phases were separated
3. washThe organic phase was washed with brine (2×250 mL)
4. dry with materialdried (Na2SO4)
5. concentrationconcentrated
6. dissolutionThe resultant oil was dissolved in DMF (570 mL)
7. temperatureheated at 70° C. overnight
8. temperatureThe mixture was cooled to room temperature
9. customevaporated
10. additionthe residual slurry was poured into brine (500 mL)
11. extractionextracted with ether (4×500 mL)
12. washThe combined organic extracts were washed with brine (2×100 mL)
13. dry with materialdried (Na2SO4)
14. concentrationconcentrated
15. filtrationThe crude material was filtered through a short plug of silica gel (CH2Cl2)

ORD record

ord-fbb5dc5c23f645bbba8ee8af98953175

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06750348B1