Cesium carbonate → Methyl 4-(2-fluoro-4-methoxyphenyl)-7-vinylquinoline-2-carboxylate

HRID 922810Notes

Reaction equation

HRID 922810 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:17]=3[F:24])=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[N:9]2)=[CH:4][CH:3]=1.[CH:25]([B-](F)(F)F)=[CH2:26].[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:25]([C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:17]=3[F:24])=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[N:9]2)=[CH:4][CH:3]=1)=[CH2:26]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 23679353Potassium vinyltrifluoroborateHCID 89543854Methyl 7-chloro-4-(2-fluoro-4-methoxyphenyl)quinoline-2-carboxylate

Product 1

HCID 89543754Methyl 4-(2-fluoro-4-methoxyphenyl)-7-vinylquinoline-2-carboxylateYield 71.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

Methyl 7-chloro-4-(2-fluoro-4-methoxyphenyl)quinoline-2-carboxylate (1.8 g, 5.21 mmol) was dissolved in dioxane (23.43 ml), degassed 10 minutes with N2. Added potassium vinyltrifluoroborate (1.395 g, 10.41 mmol), palladium(II) acetate (0.088 g, 0.390 mmol), 2-bicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.321 g, 0.781 mmol) and cesium carbonate (5.09 g, 15.62 mmol) followed by degassed water (2.60 ml). Degassed with N2 for another 10 minutes and then the mixture was stirred at 85° C. for 1 hour. Reaction was complete. The reaction mixture was cooled to ambient temperature and then diluted with EtOAc. Partitioned EtOAc with water, washed EtOAc extract with brine, dried using anhy. MgSO4 and then concentrated. The residue was purified by column chromatography on silica gel, eluting with hexanes to EtOAc to afford methyl 7-ethenyl-4-(2-fluoro-4-methoxyphenyl)quinoline-2-carboxylate (1.25 g, 3.71 mmol, 71.2% yield) as a yellow solid.

Workup

  1. customdegassed 10 minutes with N2
  2. customby degassed water (2.60 ml)
  3. customDegassed with N2 for another 10 minutes
  4. customReaction
  5. temperatureThe reaction mixture was cooled to ambient temperature
  6. washPartitioned EtOAc with water, washed EtOAc
  7. extractionextract with brine
  8. customdried
  9. concentrationMgSO4 and then concentrated
  10. customThe residue was purified by column chromatography on silica gel
  11. washeluting with hexanes to EtOAc

Sources & evidence

ORD record
ord-d5b02202dfb6450d87034218ebdab60a
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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