Potassium Fluoride → HCID 13784691, compound
Reaction equation
N([O-])=O.[Na+].[F:5][B-](F)(F)F.[Na+].Cl[C:12]1[C:19]([Cl:20])=[C:18](Cl)[C:17]([F:22])=[CH:16][C:13]=1[C:14]#[N:15].[F-:23].[K+]>CS(C)=O>[Cl:20][C:19]1[C:12]([F:5])=[C:13]([CH:16]=[C:17]([F:22])[C:18]=1[F:23])[C:14]#[N:15]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 corresponding 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-330f55c398084380a21ed3bc9f782a5c
- Source dataset
- uspto-grants-1997_05
- Patent number
- US05631266
Reaction notes
Loading…