Sodium Carbonate → 5'-Bromo-4-(ethylsulfonyl)-2,2'-difluorobiphenyl

HRID 1846030Notes

Reaction equation

HRID 1846030 reaction equation
[CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9](B2OC(C)(C)C(C)(C)O2)=[C:8]([F:21])[CH:7]=1)(=[O:5])=[O:4])[CH3:2].[Br:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[C:25](I)[CH:24]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.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]>[Br:22][C:23]1[CH:24]=[CH:25][C:26]([F:29])=[C:27]([C:9]2[CH:10]=[CH:11][C:6]([S:3]([CH2:1][CH3:2])(=[O:4])=[O:5])=[CH:7][C:8]=2[F:21])[CH:28]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27827504-Bromo-1-fluoro-2-iodobenzeneHCID 86723254HCID 86723254, compound

Product 1

HCID 867232535'-Bromo-4-(ethylsulfonyl)-2,2'-difluorobiphenylYield 57%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-[4-(ethylsulfonyl)-2-fluorophenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Preparation 45, 102 mg, 0.33 mmol) and 4-bromo-1-fluoro-2-iodobenzene (108 mg, 0.36 mmol) in toluene (0.56 mL) and ethanol (0.14 mL) was added aqueous Na2CO3 solution (1M, 0.55 mL, 0.55 mmol). A stream of nitrogen gas was bubbled through the reaction mixture for 5 minutes. Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (13 mg, 0.016 mmol) was then added, and the mixture was heated at 80° C. for 1 hour. The reaction mixture was cooled, diluted with water (20 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and the filtrate was evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with heptane:EtOAc 100:0 to 70:30 to afford the title compound as a light yellow solid in 57% yield, 67 mg.

Workup

  1. customA stream of nitrogen gas was bubbled through the reaction mixture for 5 minutes
  2. temperatureThe reaction mixture was cooled
  3. extractionextracted with EtOAc (3×20 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customthe filtrate was evaporated in vacuo
  8. customThe residue was purified by silica gel column chromatography
  9. washeluting with heptane:EtOAc 100:0 to 70:30

Sources & evidence

ORD record
ord-cacd451e5437456baff41085aa152da3
Source dataset
uspto-grants-2015_02
Patent number
US08952008B2

Reaction notes

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