Dichloromethane → HCID 58127393, compound

HRID 1623240Notes

Reaction equation

HRID 1623240 reaction equation
FC(F)(F)S(O[C:7]1[C:12]([F:13])=[CH:11][CH:10]=[C:9]([F:14])[N:8]=1)(=O)=O.[Cl:17][C:18]1[C:19](B(O)O)=[CH:20][C:21]([F:24])=[N:22][CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+].C(Cl)Cl>C1COCC1.CCOC(C)=O.O.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]>[Cl:17][C:18]1[C:19]([C:7]2[C:12]([F:13])=[CH:11][CH:10]=[C:9]([F:14])[N:8]=2)=[CH:20][C:21]([F:24])=[N:22][CH:23]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 44754822(5-Chloro-2-fluoropyridin-4-yl)boronic acidHCID 86650604Methanesulfonic acid, 1,1,1-trifluoro-, 3,6-difluoro-2-pyridinyl ester

Product 1

HCID 58127393HCID 58127393, compoundYield 85.5%

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

A mixture of 3,6-difluoropyridin-2-yl trifluoromethanesulfonate (3.50 g, 13.30 mmol) and 5-chloro-2-fluoropyridine-4-boronic acid (3.27 g, 18.62 mmol) in THF (27 ml) was degassed by bubbling Argon gas for 10 min. Aqueous sodium carbonate (13.30 ml, 26.6 mmol) and PdCl2(dppf).CH2Cl2 adduct (0.652 g, 0.798 mmol) were added, and the mixture was degassed for an additional 5 min. The resulting reaction mixture was stirred at about 100° C. for 2 hr in a sealed vessel. The reaction mixture was cooled to ambient temperature, diluted with EtOAc and water. The separated organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The resulting residue was purified by column chromatography over silica gel (heptanes/ethyl acetate gradient) to yield 2.78 g (85% yield) of 5′-chloro-2′,3,6-trifluoro-2,4′-bipyridine as a crystalline solid. LCMS (m/z): 244.9 [M+H]+; retention time=0.86 min.

Workup

  1. customwas degassed
  2. customby bubbling Argon gas for 10 min
  3. customthe mixture was degassed for an additional 5 min
  4. customThe resulting reaction mixture
  5. temperatureThe reaction mixture was cooled to ambient temperature
  6. dry with materialThe separated organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was purified by column chromatography over silica gel (heptanes/ethyl acetate gradient)

Sources & evidence

ORD record
ord-deaa685021424da79315e0860e7f6771
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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