Process for 6,7-dihydro-9-fluoro-5-methyl-1-oxo-1H,5H-benzo(ij)quinolizine-2-carboxy lic acid
AssigneeMinnesota Mining and Manufacturing Company
InventorsCharles M. Leir, Kirk G. Hedberg
Life of this patent
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Abstract
An improved process for preparing the antimicrobial compound flumequine is disclosed. The first step of the process comprises reacting 4-fluoroaniline with crotonaldehyde under acidic conditions at a temperature between 50.degree. and 60.degree. C. In the second step, the product of the first step is treated to provide a mixture of 6-fluoroquinaldine and 6-fluorotetrahydroquinaldine. This mixture is then treated with base in the presence of weak acid followed by reducing to provide 6-fluorotetrahydroquinaldine. This compound is then treated according to known procedures to form flumequine.
Claims6
A process for the preparation of flumequine comprising:
- a. reacting 4-fluoroaniline with a reactant selected from the group consisting of crotonaldehyde, a precursor for crotonaldehyde which generates crotonaldehyde under acidic conditions, and an alcoholic solution of crotonaldehyde or said precursor for crotonaldehyde in the presence of dilute aqueous acid between about 50.degree. and 60.degree. C. to provide a compound of the formula ##STR4## wherein R is hydrogen or alkyl having one, two or three carbon atoms;
- b. heating the product of step (a) to provide a mixture of 6-fluoroquinaldine and 6-fluorotetrahydroquinaldine as acid salts;
- c. treating said acid salts with base in the presence of weak acid followed by reducing the mixture to provide 6-fluorotetrahydroquinaldine;
- d. condensing said 6-fluorotetrahydroquinaldine with a dialkyl alkoxymethylenemalonate to provide a compound of the formula ##STR5## e. cyclizing the product of step (d) by heating in the presence of polyphosphoric acid followed by saponifying to provide flumequine.
A process for the preparation of flumequine comprising:
- a. reacting 4-fluoroaniline with an alcoholic solution of crotonaldehyde in the presence of dilute aqueous acid between about 50.degree. and 60.degree. C. to provide a compound of the formula ##STR6## wherein R is hydrogen or alkyl having one, two, or three carbon atoms;
- b. heating the product of step (a) to provide a mixture of 6-fluoroquinaldine and 6-fluorotetrahydroquinaldine as acid salts;
- c. treating said acid salts with base in the presence of weak acid followed by reducing the mixture to provide 6-fluorotetrahydroquinaldine;
- d. condensing said 6-fluorotetrahydroquinaldine with a dialkyl alkoxymethylenemalonate to provide a compound of the formula ##STR7## e. cyclizing the product of step (d) by heating in the presence of polyphosphoric acid followed by saponifying to provide flumequine.
A process for the preparation of 6-fluorotetrahydroquinaldine comprising:
- a. reacting 4-fluoroaniline with a reactant selected from the group consisting of crotonaldehyde, a precursor for crotonaldehyde which generates crotonaldehyde under acidic conditions, and an alcoholic solution of crotonaldehyde or said precursor for crotonaldehyde in the presence of dilute aqueous acid between about 50.degree. and 60.degree. C. to provide a compound of the formula ##STR9## wherein R is hydrogen or alkyl having one, two or three carbon atoms;
- b. heating the product of step (a) in dilute acid to provide a mixture of 6-fluoroquinaldine and 6-fluorotetrahydroquinaldine as acid salts;
- c. treating said acid salts with base in the presence of weak acid followed by reducing the mixture to form 6-fluorotetrahydroquinaldine.
Dependencies are inferred from the claim text.