1,4-Dioxane → Methyl 4-(2-fluoro-4-methoxyphenyl)-7-(prop-1-en-2-yl)quinoline-2-carboxylate

HRID 922813Notes

Reaction equation

HRID 922813 reaction equation
C(B1O[C:9]([CH3:11])([CH3:10])[C:6]([CH3:8])([CH3:7])O1)(C)=C.ClC1C=[C:22]2[C:17]([C:18]([C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:29]=3[F:36])=[CH:19][C:20]([C:24]([O:26][CH3:27])=[O:25])=[N:21]2)=[CH:16]C=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2].O>[F:36][C:29]1[CH:30]=[C:31]([O:34][CH3:35])[CH:32]=[CH:33][C:28]=1[C:18]1[C:17]2[C:22](=[CH:11][C:9]([C:6]([CH3:7])=[CH2:8])=[CH:10][CH:16]=2)[N:21]=[C:20]([C:24]([O:26][CH3:27])=[O:25])[CH:19]=1

Participants

9

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolaneHCID 89543854Methyl 7-chloro-4-(2-fluoro-4-methoxyphenyl)quinoline-2-carboxylate

Product 1

HCID 89543695Methyl 4-(2-fluoro-4-methoxyphenyl)-7-(prop-1-en-2-yl)quinoline-2-carboxylateYield 64.9%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 12976736Bis(ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane);iron(2+)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Isopropenylboronic acid pinacol ester (2.67 g, 15.91 mmol), methyl 7-chloro-4-(2-fluoro-4-methoxyphenyl)quinoline-2-carboxylate (5 g, 14.46 mmol), potassium phosphate tribasic (9.21 g, 43.4 mmol) and dioxane (43.8 ml)/water (4.38 ml) were combined and then degassed with nitrogen for 5 minutes. Added palladium(II) acetate (0.243 g, 1.085 mmol) and 1,1′-bis(di-tert-butylphosphino)ferrocene (0.515 g, 1.085 mmol) and then heated to 85° C. for 4 hours. Reaction was complete and was allowed to cool to ambient temperature. The mixture was diluted with EtOAc and then washed with H2O, brine, dried (MgSO4) and concentrated. The residue was purified by column chromatography on silica gel, eluting with hexanes to EtOAc to afford methyl 4-(2-fluoro-4-methoxyphenyl)-7-(prop-1-en-2-yl)quinoline-2-carboxylate (3.3 g, 9.39 mmol, 64.9% yield) as a yellow solid.

Workup

  1. customdegassed with nitrogen for 5 minutes
  2. customReaction
  3. washwashed with H2O, brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel
  7. washeluting with hexanes to EtOAc

Sources & evidence

ORD record
ord-43238e11c3ca4dabb90d3d2e88ddb5f0
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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