Methanol → HCID 12802762, compound

A mixture of 1-o-chlorobenzyl-4-methyl-6-methoxy-2-oxo-1,2-dihydroquinoline (2.5 g.), oil-free sodium hydride (obtained from 2.5 g. of a 50% w/w suspension as described in Example 1) and diethyl carbonate (50 ml.) was heated over 1 hour to reflux and the reflux maintained for 3 hours. The mixture was cooled and treated with methanol (2 ml.) to destroy excess sodium hydride. Ether (200 ml.) was added and the yellow precipitate was filtered off, washed with ether (50 ml.), and dried, and was then suspended in dimethylformamide (100 ml.) containing methyl iodide (4 ml.). After 24 hours standing at room temperature, the mixture was diluted with water (200 ml.) and the aqueous mixture extracted with ether (3×100 ml.). The combined ethereal extracts were washed with water (2×100 ml.), and dried with magnesium sulphate, and the ether was evaporated. The residue, which comprised diethyl α-(1-o-chlorobenzyl-6-methoxy-2-oxo-1,2-dihydroquinol-4-yl)-α-methylmalonate, was dissolved in a solution of potassium hydroxide (3.6 g.) in water (4 ml.) and ethanol (100 ml.). The mixture was refluxed for 1 hour, cooled, and diluted with N-hydrochloric acid (100 ml.). The resulting mixture was filtered, and the solid residue washed with water and crystallised from methanol (100 ml.) to give α-(1-o-chlorobenzyl-6-methoxy-2-oxo-1,2-dihydroquinol-4-yl)propionic acid, m.p. 187°-188° C. in 48% yield.

1. customobtained from 2.5 g
2. temperaturewas heated over 1 hour
3. temperatureto reflux
4. temperaturethe reflux maintained for 3 hours
5. temperatureThe mixture was cooled
6. customto destroy excess sodium hydride
7. additionEther (200 ml.) was added
8. filtrationthe yellow precipitate was filtered off
9. washwashed with ether (50 ml.)
10. customdried
11. additioncontaining methyl iodide (4 ml.)
12. additionthe mixture was diluted with water (200 ml.)
13. extractionthe aqueous mixture extracted with ether (3×100 ml.)
14. washThe combined ethereal extracts were washed with water (2×100 ml.)
15. dry with materialdried with magnesium sulphate
16. customthe ether was evaporated
17. dissolutionwas dissolved in a solution of potassium hydroxide (3.6 g.) in water (4 ml.) and ethanol (100 ml.)
18. temperatureThe mixture was refluxed for 1 hour
19. temperaturecooled
20. additiondiluted with N-hydrochloric acid (100 ml.)
21. filtrationThe resulting mixture was filtered
22. washthe solid residue washed with water
23. customcrystallised from methanol (100 ml.)

ORD record

ord-55c85a580b8a412aaf936c84ac3946b9

Source dataset

uspto-grants-1980_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04187310