US4301289A
Expired / Lapsed
US
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Process for 6,7-dihydro-9-fluoro-5-methyl-1-oxo-1H,5H-benzo(ij)quinolizine-2-carboxylic acid
Assignee: 3M Co
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Filing: 1980-02-19
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Granted: 1981-11-17
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Expires: 2000-02-19
Abstract
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° and 60° 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.
Inventors
- 👤 Charles M. Leir
- 👤 Kirk G. Hedberg
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 03:21
CPC Classifications
C; C07; C07D; C07D215/00; C07D215/02; C07D215/16; C07D215/20; C07D215/22; C07D215/233; C07D215/18; C07D455/00; C07D455/03; C07D455/04
Claims Analysis
Total Claims: 9
Claim 1
Independent Claim
152 words
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° and 60° 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.
Claim 2
Dependent Claim
152 words
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° and 60° 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.
Claim 3
Dependent Claim
127 words
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° and 60° 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.
Claim 4
Dependent Claim
127 words
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° and 60° 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.
Claim 5
Dependent Claim
24 words
The process according to claim 2 wherein said reactant in step (a) is a methanolic solution of crotonaldehyde and said compound provided is ##STR8##
Claim 6
Dependent Claim
16 words
The process according to claim 1 wherein said dilute aqueous acid in step (a) is hydrochloric.
Claim 7
Dependent Claim
15 words
The process according to claim 1 wherein said dialkyl alkyloxymethylenemalonate of step (d) is diethylethoxymethylenealonate.
Claim 8
Dependent Claim
118 words
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° and 60° 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.
Claim 9
Dependent Claim
118 words
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° and 60° 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.
References Cited (Backward Citations)
US3896131A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1984-11-16 | 1985-05-18 | 1985-11-17 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1988-11-16 | 1989-05-18 | 1989-11-17 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1992-11-16 | 1993-05-18 | 1993-11-17 | $7700.00 | Window Closed / Lapsed |