Sodium hydride → Ethyl 1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 1762736Notes

Reaction equation

HRID 1762736 reaction equation
Cl[C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[C:10](=[O:22])[C:11](=[CH:17][NH:18][CH:19]1[CH2:21][CH2:20]1)[C:12]([O:14][CH2:15][CH3:16])=[O:13].[H-].[Na+]>CN(C)C=O>[CH:19]1([N:18]2[C:2]3[C:3](=[CH:4][C:5]([F:9])=[C:6]([F:8])[CH:7]=3)[C:10](=[O:22])[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:17]2)[CH2:21][CH2:20]1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 178471872HCID 178471872, compound

Product 1

HCID 9817544Ethyl 1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In accordance with the above reaction scheme, a solution of 2-chloro-4,5-difluorobenzoic acid (V) in acetonitrile containing a catalytic amount of dimethylformamide is reacted under an inert atmosphere with the dropwise addition of oxalyl chloride, giving 2-chloro-4,5-difluorobenzoic acid chloride (VI) which is dissolved in diethyl ether and slowly added to a cold solution of magnesium diethylmalonate, followed by the addition to ice water and acidification to pH 2.5, giving (2-chloro-4,5-difluorobenzoyl)propanedioic acid diethyl ester (VII). A solution of compound (VII) in p-dioxane and water is heated at reflux, then evaporated and distilled, giving 2-chloro-4,5-difluoro-β-oxobenzenepropanoic acid ethyl ester (VIII). A solution of compound (VIII) and triethyl orthoformate in acetic anhydride is heated at 150° C. for 2 hours, giving 2-chloro-α-(ethoxymethylene)-4,5-difluoro-β-oxobenzenepropanoic acid, ethyl ester (IX). Cyclopropylamine is added to a solution of compound (IX) in ethanol, giving 2-chloro-α-[(cyclopropylamino)methylene]-4,5-difluoro-β-oxobenzenepropanoic acid, ethyl ester (X). Compound (X) is reacted with sodium hydride in dry dimethylformamide under an inert atmosphere with heat, giving 1-cyclopropyl-6,7-difluoro- 1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, ethyl ester (XI). Ester (XI) is then refluxed with acid, giving the desired 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (XII).

Workup

  1. temperaturewith heat

Sources & evidence

ORD record
ord-54faefad601549b8a271009e989ff802
Source dataset
uspto-grants-1989_05
Patent number
US04833270

Reaction notes

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