Acetic Anhydride → Ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate
Reaction equation
[Cl:1][C:2]1[C:3]([F:18])=[C:4]([CH:13]=[C:14]([F:17])[C:15]=1[F:16])[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])=[O:6].[CH:19](OCC)(OCC)[O:20][CH2:21][CH3:22].C(OC(=O)C)(=O)C>>[Cl:1][C:2]1[C:3]([F:18])=[C:4]([CH:13]=[C:14]([F:17])[C:15]=1[F:16])[C:5]([C:7](=[CH:19][O:20][CH2:21][CH3:22])[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[O:6]Participants
Procedure
The reduction of 2,3,4-trichloro-5-fluoronitrobenzene (i) with Fe--HCI in hot water gives 2,3,4-trichloro-5-fluoroaniline (ii), which, by diazotization with NaNO2 --HCI and reaction with sodium tetra-fluoroborate and cuprous cyanide, is converted to 2,3,4-trichloro-5-fluorobenzonitrile (iii). The reaction of (iii) with KF in DMSO at 140° affords 3-chloro-2,4,5-trifluorobenzonitrile (iv), which, by hydrolysis with 30% HBr in refluxing acetic acid, gives 3-chloro-2,4,5-trifluorobenzamide (v). The hydrolysis of (v) with 18N H2SO4 at 135° yields the corrsponding benzoic acid (vi), which is treated with refluxing SOCl2 to afford the acyl chloride (vii). The condensation of (vii) with diethyl malonate (viii) by means of Mg-ethanol in hot toluene gives diethyl 3-chloro-2,4,5-trifluorobenzoylmalonate (ix), which is partially decarboxylated with p-toluenesulfonic acid in refluxing water to give ethyl 3-chloro-2,4,5-trifluorobenzoylacetate (x). The condensation of (x) with triethyl orthoformate (xi) in refluxing acetic anhydride yields ethyl 2-(3-chloro-2,4,5-trifluorobenzoyl)-3-ethoxyacrylate (xii), which is treated with cyclopropylamine (xiii) in ethanol to afford ethyl 2-(3-chloro-2,4,5-trifluorobenzoyl)-3-(cyclopropylamino)acrylate (xiv). The cyclization of (xiv) by means of NaF in DMF at 150° gives ethyl 8-chloro-1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (xv), which is hydrolyzed with H2SO4 in refluxing water-acetic acid to the corresponding carboxylic acid (xvi).
Sources & evidence
- ORD record
- ord-3c7441a0ad7d4a1ab03a48dc0687e22d
- Source dataset
- uspto-grants-1996_03
- Patent number
- US05498615
Reaction notes
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