Dichloromethane → HCID 86726470, compound

HRID 1430079Notes

Reaction equation

HRID 1430079 reaction equation
Br[C:2]1[C:11]2[C:6](=[C:7]([F:12])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]([NH:15][C@H:16]2[CH2:21][CH2:20][CH2:19][CH2:18][C@@H:17]2[OH:22])=[O:14])[CH:3]=1.[CH:23]([B-](F)(F)F)=[CH2:24].[K+].C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.C1COCC1>[CH:23]([C:2]1[C:11]2[C:6](=[C:7]([F:12])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]([NH:15][C@H:16]2[CH2:21][CH2:20][CH2:19][CH2:18][C@@H:17]2[OH:22])=[O:14])[CH:3]=1)=[CH2:24]

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 23679353Potassium vinyltrifluoroborateHCID 71042493HCID 71042493, compound

Product 1

HCID 86726470HCID 86726470, compound

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-bromo-8-fluoro-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide (C7) (1.88 g, 5.12 mmol) in 10:1 THF:H2O (22 mL) was added potassium vinyltrifluoroborate (2.06 g, 15.4 mmol) and cesium carbonate (3.34 g, 10.2 mmol). The reaction was placed under N2(g), and [1,1′-bis(diphenylphosphino)-ferrocene]dichloro palladium(II), complex with dichloromethane (0.100 g, 0.122 mmol) was added. The mixture was heated to 100° C. for 3 h, then cooled to RT and diluted with ethyl acetate. The organic solution was washed with saturated aqueous sodium bicarbonate (1×) and brine (1×), dried over sodium sulfate, filtered, and concentrated in vacuo. The resultant residue was purified via silica gel chromatography eluting with 0-5% methanol in dichloromethane to provide 4-ethenyl-8-fluoro-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide (C8) that gave a mass ion (ES+) of 315.1 for M+H+.

Workup

  1. temperaturecooled to RT
  2. washThe organic solution was washed with saturated aqueous sodium bicarbonate (1×) and brine (1×)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified via silica gel chromatography
  7. washeluting with 0-5% methanol in dichloromethane

Sources & evidence

ORD record
ord-d16b43124a8740f6aa3ad9b4508eb367
Source dataset
uspto-grants-2015_01
Patent number
US08940765B2

Reaction notes

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