1-Bromo-3-chlorobenzene → 3'-Chlorobiphenyl-4-yl trifluoromethyl ether

HRID 1880594Notes

Reaction equation

HRID 1880594 reaction equation
C([O-])([O-])=O.[K+].[K+].Br[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[CH:9]=1.[F:15][C:16]([F:28])([F:27])[O:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=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.COCCOC>[F:15][C:16]([O:17][C:18]1[CH:19]=[CH:20][C:21]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[CH:9]=2)=[CH:22][CH:23]=1)([F:27])[F:28]

Participants

6

Reactant 3

HCID 79281-Bromo-3-chlorobenzeneHCID 11430Potassium CarbonateHCID 27343864-(Trifluoromethoxy)phenylboronic acid

Product 1

HCID 571206723'-Chlorobiphenyl-4-yl trifluoromethyl ether

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of DME (40 mL) and 2M K2CO3 (40 mL) containing 1-bromo-3-chlorobenzene (2.53 g, 13.21 mol), 4-(trifluoromethoxy)phenyl boronic acid (4 g, 19.4 mmol) and Pd(PPh3)4 (0.76 g, 0.66 mmol) was refluxed under an argon atmosphere until no starting material remained by HPLC analysis. The solution was concentrated (to remove excess DME) and partitioned between water and ethyl acetate. The organic phase was washed with 1N NaOH, water (2×) and brine. The solution was then dried over MgSO4, filtered and concentrated. The residue was purified by silica gel chromatography using a hexanes/ethyl acetate gradient to give the title compound. LCMS1 4.23 min.

Workup

  1. temperaturewas refluxed under an argon atmosphere until no starting material
  2. concentrationThe solution was concentrated
  3. custom(to remove excess DME)
  4. custompartitioned between water and ethyl acetate
  5. washThe organic phase was washed with 1N NaOH, water (2×) and brine
  6. dry with materialThe solution was then dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-46302d62b2294ad09631e11a46842dbd
Source dataset
uspto-grants-2012_11
Patent number
US08318760B2

Reaction notes

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