Cesium carbonate → Methyl 7-[(2,5-dioxopyrrolidin-1-yl)methyl]-8-fluoro-4-(4-fluorophenyl)quinoline-2-carboxylate

HRID 922799Notes

Reaction equation

HRID 922799 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].[C:7]1(=[O:13])[NH:11][C:10](=[O:12])[CH2:9][CH2:8]1.Br[CH2:15][C:16]1[C:25]([F:26])=[C:24]2[C:19]([C:20]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)=[CH:21][C:22]([C:27]([O:29][CH3:30])=[O:28])=[N:23]2)=[CH:18][CH:17]=1>CN(C=O)C>[O:13]=[C:7]1[CH2:8][CH2:9][C:10](=[O:12])[N:11]1[CH2:15][C:16]1[C:25]([F:26])=[C:24]2[C:19]([C:20]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)=[CH:21][C:22]([C:27]([O:29][CH3:30])=[O:28])=[N:23]2)=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11439SuccinimideHCID 89554976Methyl 7-(bromomethyl)-8-fluoro-4-(4-fluorophenyl)quinoline-2-carboxylate

Product 1

HCID 89554967Methyl 7-[(2,5-dioxopyrrolidin-1-yl)methyl]-8-fluoro-4-(4-fluorophenyl)quinoline-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Cs2CO3 (1.745 g, 5.35 mmol) was added to a solution of Succinimide (0.292 g, 2.94 mmol) and methyl 7-(bromomethyl)-8-fluoro-4-(4-fluorophenyl)quinoline-2-carboxylate 7-10 (1.05 g, 2.68 mmol) in DMF (13.39 ml) and the reactant stirred at rt for 30 min. The reaction was quenched with KH2PO4 (saturated) and the mixture was extracted with ethyl acetate (×3). The combined organic fractions were dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The solvent was removed in vacuo and the residue purified by column chromatography on a silica gel column, eluting with EtOAc/hexane (0-100%) to afford Methyl 7-[(2,5-dioxopyrrolidin-1-yl)methyl]-8-fluoro-4-(4-fluorophenyl)quinoline-2-carboxylate 7-11 as a white solid, LCMS shows the compound is 90% pure, LRMS m/z (M+H)+ 411.2 found, 411.1 required.

Workup

  1. customThe reaction was quenched with KH2PO4 (saturated)
  2. extractionthe mixture was extracted with ethyl acetate (×3)
  3. dry with materialThe combined organic fractions were dried (MgSO4)
  4. filtrationfiltered
  5. customthe solvent was evaporated under reduced pressure
  6. customThe solvent was removed in vacuo
  7. customthe residue purified by column chromatography on a silica gel column
  8. washeluting with EtOAc/hexane (0-100%)

Sources & evidence

ORD record
ord-ee46c7dcb6894f8b95e5308bd4eca2a9
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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