Potassium Carbonate → 1-(4'-Chloro-2'-fluoro-1,1'-biphenyl-2-yl)ethanone

HRID 2181925Notes

Reaction equation

HRID 2181925 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1B(O)O)(=[O:3])[CH3:2].[Cl:13][C:14]1[CH:19]=[CH:18][C:17](I)=[C:16]([F:21])[CH:15]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:1](=[O:3])[CH3:2])=[C:16]([F:21])[CH:15]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27343092-Acetylphenylboronic acidHCID 27365624-Chloro-2-fluoro-1-iodobenzene

Product 1

HCID 224823221-(4'-Chloro-2'-fluoro-1,1'-biphenyl-2-yl)ethanoneYield 54%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
85 °C

Procedure

2-Acetylphenylboronic acid (5 g, 30.5 mmol) and 4-chloro-2-fluoroiodobenzene (8.6 g, 33.5 mmol) were dissolved in a toluene/ethanol mixture (6:1, 175 mL). An aqueous solution of potassium carbonate (2 M, 60 mL) and tetrakis(triphenylphosphine)palladium (0) (1.06 g, 0.91 mmol) were added to the solution and the entire mixture was degassed using vacuum and stirring with intermittent nitrogen purge. The mixture was heated at 85° C. with stirring for 14 hours. The mixture was allowed to cool and then water was added. The organic phase was separated from the aqueous phase and the aqueous phase was extracted with ethyl acetate (3×100 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to a crude oil. The crude oil was purified by preparative liquid chromatography on a Biotage® 40 Mi column of prepacked silica gel (90 g), eluting with a gradient of 5%-20% methyl tert-butyl ether in hexane, to afford the desired product (4.07 g, 54%) as a yellow oil;

Workup

  1. customthe entire mixture was degassed
  2. custompurge
  3. stirringwith stirring for 14 hours
  4. temperatureto cool
  5. additionwater was added
  6. customThe organic phase was separated from the aqueous phase
  7. extractionthe aqueous phase was extracted with ethyl acetate (3×100 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated to a crude oil
  11. customThe crude oil was purified by preparative liquid chromatography on a Biotage® 40 Mi column of prepacked silica gel (90 g)
  12. washeluting with a gradient of 5%-20% methyl tert-butyl ether in hexane

Sources & evidence

ORD record
ord-57e1846c73a143b399fcb45d1e588093
Source dataset
uspto-grants-2005_05
Patent number
US06894061B2

Reaction notes

Loading…