Dimethylformamide → 4-[2-(3-Methoxyphenyl)-ethoxy]-quinoline-6-carbaldehyde

To a solution of 2-(3-methoxyphenyl)-ethanol (359 mg, 2.36 mmol) in DMF (13 mL) was added sodium hydride (62.3 mg, 2.59 mmol) at 0° C. and stirred for 15 min at this temperature. Then, a solution of butyl (4-chloroquinolin-6-ylmethylene)-amine (preparation was described in example 27b) (300 mg, 1.18 mmol) in DMF (3 mL) was added at 0° C. After addition, the reaction mixture was allowed to warm to room temperature and stirred for 30 min. During this period, the color of the solution was changed from white to black and then to brown. Then, the reaction mixture was heated to 60° C. and stirred for 15 h. After cooling to room temperature, the mixture was diluted with saturated ammonium chloride solution and the organic compound was extracted into ethyl acetate (3×50 mL). The combined extracts were washed with brine solution and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solvent was removed under the vacuum and the oily residue was dissolved in THF (3 mL) and 3 mL of HCl solution (3.0N) was added. The resulting solution was stirred for 2 h at room temperature. Then, it was neutralized with saturated sodium bicarbonate solution and the organic compound was extracted into ethyl acetate (3×50 mL). The combined extracts were washed with brine solution and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solvent was removed under the vacuum and the residue was purified by using a Biotage silica gel column chromatography to obtain 133 mg (36.7% yield) of 4-[2-(3-methoxyphenyl)-ethoxy]-quinoline-6-carbaldehyde as a light yellow solid: EI-HRMS m/e calcd for C19H17NO3 (M+) 307.1208, found 307.1204.

1. additionAfter addition
2. stirringstirred for 30 min
3. waitDuring this period
4. temperatureThen, the reaction mixture was heated to 60° C.
5. stirringstirred for 15 h
6. temperatureAfter cooling to room temperature
7. extractionthe organic compound was extracted into ethyl acetate (3×50 mL)
8. washThe combined extracts were washed with brine solution
9. dry with materialdried over anhydrous magnesium sulfate
10. filtrationAfter filtration of the drying agent
11. customthe solvent was removed under the vacuum
12. dissolutionthe oily residue was dissolved in THF (3 mL)
13. addition3 mL of HCl solution (3.0N) was added
14. stirringThe resulting solution was stirred for 2 h at room temperature
15. extractionthe organic compound was extracted into ethyl acetate (3×50 mL)
16. washThe combined extracts were washed with brine solution
17. dry with materialdried over anhydrous magnesium sulfate
18. filtrationAfter filtration of the drying agent
19. customthe solvent was removed under the vacuum
20. customthe residue was purified

ORD record

ord-38bffe0aa4f94435af1a52b5f85153e7

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07253285B2