Methanol → 1-(4'-Chloro-4-fluoro-biphen-2-yl)-ethanone

HRID 1788604Notes

Reaction equation

HRID 1788604 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9](=[O:11])[CH3:10].[Cl:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.CO.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:2]2[C:3]([C:9](=[O:11])[CH3:10])=[CH:4][C:5]([F:8])=[CH:6][CH:7]=2)=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 742994-Chlorophenylboronic acidHCID 516892Sodium BicarbonateHCID 227360801-(2-Bromo-5-fluorophenyl)ethan-1-one

Product 1

HCID 860272381-(4'-Chloro-4-fluoro-biphen-2-yl)-ethanoneYield 82.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

1-(2-Bromo-5-fluoro-phenyl)-ethanone (868 mg, 4 mmol), p-chlorophenylboronic acid (768 mg, 1.2 eq.), and tetrakis (triphenylphosphine)palladium(0) (473 mg, 0.1 eq.), were dissolved in 25 mL toluene, 6 mL methanol and 2.5 mL sat. sodium bicarbonate solution. After degassing/sonicating the solution, the sealed reaction vessel was heated to 80° C. overnight. The cooled solution was separated between ethyl acetate and water; the aqueous phase extracted two more times with ethyl acetate, and the organic fractions were combined, dried with sodium sulfate and evaporated. Silica gel chromatography (5:1 hexanes/ethyl acetate) gave 1-(4′-chloro-4-fluoro-biphen-2-yl)-ethanone (821 mg).

Workup

  1. customAfter degassing/sonicating the solution
  2. customthe sealed reaction vessel
  3. customThe cooled solution was separated between ethyl acetate and water
  4. extractionthe aqueous phase extracted two more times with ethyl acetate
  5. dry with materialdried with sodium sulfate
  6. customevaporated

Sources & evidence

ORD record
ord-6a81c8e2a4db4ee29e2e549c8369a27e
Source dataset
uspto-grants-2009_03
Patent number
US07511145B2

Reaction notes

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