(3,5-Difluorophenyl)boronic acid → 1-(6-Bromo-4-chloro-3',5'-difluorobiphenyl-2-yl)ethanone

HRID 510913Notes

Reaction equation

HRID 510913 reaction equation
[Na].FC(F)(F)S(O[C:8]1[C:13]([Br:14])=[CH:12][C:11]([Cl:15])=[CH:10][C:9]=1[C:16](=[O:18])[CH3:17])(=O)=O.[F:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[C:26]([F:28])[CH:27]=1>O.C1(C)C=CC=CC=1.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>[Br:14][C:13]1[C:8]([C:24]2[CH:23]=[C:22]([F:21])[CH:27]=[C:26]([F:28])[CH:25]=2)=[C:9]([C:16](=[O:18])[CH3:17])[CH:10]=[C:11]([Cl:15])[CH:12]=1

Participants

7

Reactant 3

HCID 2734338(3,5-Difluorophenyl)boronic acidHCID 5360545SodiumHCID 866668322-Acetyl-6-bromo-4-chlorophenyl trifluoromethanesulfonate

Product 1

HCID 679692721-(6-Bromo-4-chloro-3',5'-difluorobiphenyl-2-yl)ethanoneYield 89.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of sodium hydrogenecarbonate (2.0 g, 23 mmol) in water (50 mL) was treated with a solution of 2-acetyl-6-bromo-4-chlorophenyl trifluoromethanesulfonate (4.5 g, 12 mmol) in toluene (50 mL) followed by (3,5-difluorophenyl)boronic acid (2.0 g, 13 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.67 g, 0.58 mmol). The reaction mixture was degassed with nitrogen for 5 min and heated at 80° C. overnight. The reaction mixture was diluted with water and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with sodium bicarbonate, water, and brine, dried with sodium sulfate, filtered, and concentrated to a crude residue. Purification by flash column chromatography using ethyl acetate in hexanes (0%-10%) gave the desired product (3.7 g, 82%). LCMS for C14H9BrClF2O (M+H)+: m/z=344.9, 346.9. Found: 344.9, 346.8.

Workup

  1. customThe reaction mixture was degassed with nitrogen for 5 min
  2. additionThe reaction mixture was diluted with water
  3. extractionextracted with ethyl acetate (2×100 mL)
  4. washThe combined organic layers were washed with sodium bicarbonate, water, and brine
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to a crude residue
  8. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-d0747f37c2e0470a905b96db01b1c0a7
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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