Diethyl Malonate → 1-Cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic Acid Ethyl Ester

HRID 483290Notes

Reaction equation

HRID 483290 reaction equation
F[C:2]1[C:10]([F:11])=[C:9]([F:12])[C:8]([F:13])=[CH:7][C:3]=1[C:4]([OH:6])=O.[Na].[C:15](Cl)(=O)C(Cl)=O.[C:21]([O:29][CH2:30][CH3:31])(=[O:28])[CH2:22][C:23](OCC)=O.[Mg].[F:33][C:34]1[C:47]([F:48])=[C:46]([F:49])[C:45]([F:50])=[CH:44][C:35]=1[C:36]([CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])=[O:37].C(OC(OCC)OCC)C.C(OC(=O)C)(=O)C.[CH:68]1([NH2:71])[CH2:70][CH2:69]1>>[CH:68]1([N:71]2[C:2]3[C:3](=[CH:7][C:8]([F:13])=[C:9]([F:12])[C:10]=3[F:11])[C:4](=[O:6])[C:22]([C:21]([O:29][CH2:30][CH3:31])=[O:28])=[CH:23]2)[CH2:70][CH2:69]1.[F:33][C:34]1[C:47]([F:48])=[C:46]([F:49])[C:45]([F:50])=[CH:44][C:35]=1[C:36]([C:38](=[CH:15][NH:71][CH:68]1[CH2:70][CH2:69]1)[C:39]([O:41][CH2:42][CH3:43])=[O:40])=[O:37]

Participants

11

Reactant 9

HCID 7761Diethyl MalonateHCID 7918Acetic AnhydrideHCID 31214Ethyl orthoformateHCID 65578Oxalyl chlorideHCID 69828CyclopropylamineHCID 2975492,3,4,5-Tetrafluorobenzoic acid2×HCID 600916Ethyl 3-oxo-(2,3,4,5-tetrafluorophenyl)propanoateHCID 5360545SodiumHCID 5462224Magnesium

Product 2

HCID 5354151-Cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic Acid Ethyl EsterHCID 178471877HCID 178471877, compound

Procedure

The starting materials for the present invention are known, or if new, may be prepared from known materials by known means. Thus, ethyl 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate is prepared as described in Belgian Pat. No. 899,399 or No. DE3318145. Alternatively, it may be prepared by a series of reactions starting from 2,3,4,5-tetrafluorobenzoic acid. The sodium salt of 2,3,4,5-tetrafluorobenzoic acid is reacted with oxalyl chloride and the product condensed with diethyl malonate in the presence of magnesium turnings to afford after hydrolysis 2,3,4,5-tetrafluorobenzoylacetic acid, ethyl ester. This compound is, in turn, treated with triethylorthoformate and acetic anhydride, followed by cyclopropylamine to afford 2-(2,3,4,5-tetrafluorobenzoyl)-3-cyclopropylamino acrylic acid, ethyl ester, which is then ring closed to give the desired starting material. The corresponding methyl ester is prepared using dimethylmalonate in the sequence described above.

Workup

  1. customif new, may be prepared
  2. customAlternatively, it may be prepared by a series of reactions
  3. customto afford

Sources & evidence

ORD record
ord-3292f44d3208476cb08631810f010c12
Source dataset
uspto-grants-1986_03
Patent number
US04578473

Reaction notes

Loading…