Sodium Carbonate → 4-Chloro-7-fluoro-3-methyl-2-(2-methylpyridin-3-yl)quinoline

HRID 1618525Notes

Reaction equation

HRID 1618525 reaction equation
Cl[C:2]1[C:11]([CH3:12])=[C:10]([Cl:13])[C:9]2[C:4](=[CH:5][C:6]([F:14])=[CH:7][CH:8]=2)[N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:21][C:22]1[C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:25]=[CH:24][N:23]=1>O1CCOCC1.CCOC(C)=O.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:13][C:10]1[C:9]2[C:4](=[CH:5][C:6]([F:14])=[CH:7][CH:8]=2)[N:3]=[C:2]([C:27]2[C:22]([CH3:21])=[N:23][CH:24]=[CH:25][CH:26]=2)[C:11]=1[CH3:12]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 164142712-Methylpyridine-3-boronic acid, pinacol esterHCID 596311082,4-Dichloro-7-fluoro-3-methylquinoline

Product 1

HCID 672852274-Chloro-7-fluoro-3-methyl-2-(2-methylpyridin-3-yl)quinoline

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 2,4-dichloro-7-fluoro-3-methylquinoline (400 mg, 1.74 mmol) in 1,4-dioxane:water (5 mL:1 mL) was added PdCl2(PPh3)2 (122 mg, 0.17 mmol), sodium carbonate (553 mg, 5.22 mmol) and 2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine. The reaction was heated at reflux overnight. After this time the reaction was diluted with EtOAc (100 mL) and water (50 mL). The separated organic layer was dried over MgSO4, filtered and evaporated in vacuo. Column chromatography (hexane:EtOAc, 1:0 to 1:1) gave 4-chloro-7-fluoro-3-methyl-2-(2-methylpyridin-3-yl)quinoline.

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux overnight
  3. dry with materialThe separated organic layer was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-9ba8a23ce27e4df09260b6431e919fc8
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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