Method for producing 8-methoxy-quinolinecarboxylic acids

1. Process for preparing 3-quinolonecarboxylic acid derivatives of the general formula

wherein

R′ and R″ together with the linking nitrogen atom form a mono- or bicyclic heterocycle which may optionally contain in all ring moieties further nitrogen, oxygen or sulphur heteroatoms and which may optionally be substituted,

wherein

R 1 represents C 1 -C 3 -alkyl, FCH 2 —CH 2 —, cyclopropyl, or represents phenyl or cyclopropyl, each of which is optionally mono- to trisubstituted by halogen,

R 2 represents C 1 -C 3 -alkyl or benzyl,

R 3 represents H, halogen, NH 2 , CH 3 ,

comprising reacting 8-halogeno-3-quinolonecarboxylic acid derivatives of the general formula

wherein

Hal represents fluorine or chlorine and R 1 , R 2 , R 3 and

 are each as defined above,

in an aliphatic or cycloaliphatic ether having 4 to 6 carbon atoms as solvent in the presence of C 1 -C 3 -alkanols or benzyl alcohol with

wherein

M represents sodium or potassium.

2. The process according to claim 1 , wherein the solvent selected is selected from the group consisting of dimethoxyethane, dioxane and tetrahydrofuran.

3. The process according to claim 2 , wherein the solvent is tetrahydrofuran.

4. The process according to claim 1 , wherein Hal represents fluorine.

5. The process according to claim 1 , wherein the (C 1 -C 3 )-alkanol is methanol.

6. The process according to claim 1 , wherein M is potassium.

7. The process according to claim 1 , wherein based on 1 equivalent of the compound of the formula

1 to 3 equivalents of the (C 1 -C 3 )-alkanol or the benzyl alcohol, and 2 to 3 equivalents of the compound of the formula

are employed.

8. The process according to claim 1 , characterized in that the reaction is carried out between 20° C. and the boiling point of the solvent at atmospheric pressure.

9. The process according to claim 1 , wherein

10. The process according to claim 1 , wherein

wherein

T represents —O— or —CH 2 — and

R 4 represents hydrogen, C 1 -C 3 -alkyl, C 2 -C 5 -oxoalkyl, —CH 2 —CO—C 6 H 5 , —CH 2 CH 2 CO 2 R 5 ,

5-methyl-2-oxo-1,3-dioxol-4-yl-methyl, —CH═CH—CO 2 R 5 or

—CH 2 CH 2 —CN,

wherein

R 5 represents hydrogen or C 1 -C 3 -alkyl,

and the formula (a) includes any mixtures of the stereoisomers (b) to (e).

11. Process for preparing

in which

R 2 represents C 1 -C 3 -alkyl or benzyl,

comprising reacting

is reacted in an aliphatic or cycloaliphatic ether having 4 to 6 carbon atoms as solvent in the presence of C 1 -C 3 -alcohols or benzyl alcohol with

wherein

M represents sodium or potassium.

12. The process according to claim 11 , wherein the solvent is selected from the group consisting of dimethoxyethane, dioxane and tetrahydrofuran.

13. The process according to claim 12 , wherein the solvent is tetrahydrofuran.

14. The process according to claim 11 , wherein the (C 1 -C 3 )-alkanol is methanol.

15. The process according to claim 11 , wherein M is potassium.

16. The process according to claim 11 , wherein, based on 1 equivalent of the compound of the formula

1 to 3 equivalents of the (C 1 -C 3 )-alkanol or the benzyl alcohol, and 2 to 3 equivalents of the compound of the formula

are employed.

17. The process according to claim 11 , wherein the reaction is carried out between 20° C. and the boiling point of the solvent at atmospheric pressure.

18. The process according to claim 11 for preparing

further comprising reacting

methanol and potassium tert-butoxide in tetrahydrofuran as solvent.

19. The process according to claim 18 , wherein, based on one equivalent of the compound of the formula

1 to 3 equivalents of methanol and 2 to 3 equivalents of potassium tert-butoxide are employed.

20. The process according to claim 18 , wherein the reaction is carried out between 20° C. and the boiling point of the solvent at atmospheric pressure.