1,3-Dibromobenzene → HCID 57825196, compound

HRID 1668720Notes

Reaction equation

HRID 1668720 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([Br:13])[CH:8]=1.[Cl:14][C:15]1[CH:16]=[C:17]([C:25](=O)[CH3:26])[CH:18]=[CH:19][C:20]=1[O:21][CH:22]([F:24])[F:23]>O1CCCC1>[Br:13][C:9]1[CH:8]=[C:7]([C:25]([C:17]2[CH:18]=[CH:19][C:20]([O:21][CH:22]([F:23])[F:24])=[C:15]([Cl:14])[CH:16]=2)=[CH2:26])[CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 79271,3-DibromobenzeneHCID 57825134HCID 57825134, compoundHCID 178418339Butyllithium

Product 1

HCID 57825196HCID 57825196, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of n-butyllithium (1.6 M in hexane, 16.4 mL, 26.2 mmol, 1.16 eq.) was added dropwise over 20 min to a solution of 1,3-dibromobenzene (3.00 mL, 24.8 mmol, 1.1 eq) in 25 mL of dry tetrahydrofuran at −78° C. and under an inert atmosphere. The white suspension formed was stirred at −78° C. for 30 min. A solution of 1-(3-chloro-4-difluoromethoxy-phenyl)-ethanone (7 g, 31.7 mmol, 1.0 eq.) in 25 mL of tetrahydrofuran was then added dropwise and the reaction stirred for 1 h. The reaction mixture was examined by LC-MS which showed the complete formation of tertiary alcohol. The solution was quenched with a saturated solution of ammonium chloride and water. 2 N HCl was then added to reach pH=5. The two phases were separated; the organic layer was dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The crude (tertiary alcohol) and a catalytic amount of p-toluenesulfonic acid were dissolved in 70 mL toluene (Dean-Stark apparatus) and the mixture was heated to reflux for 3 h. The solution was examined by TLC (cyclohexane) which showed consumption of starting material but many side products formed. Solvent was evaporated under reduced pressure and the crude residue was purified by flash chromatography eluting with cyclohexane. The desired product was obtained as yellow oil (2.2 g, Yield: 27%).

Workup

  1. customThe white suspension formed
  2. stirringthe reaction stirred for 1 h
  3. customThe solution was quenched with a saturated solution of ammonium chloride and water
  4. addition2 N HCl was then added
  5. customThe two phases were separated
  6. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. dissolutionThe crude (tertiary alcohol) and a catalytic amount of p-toluenesulfonic acid were dissolved in 70 mL toluene (Dean-Stark apparatus)
  10. temperaturethe mixture was heated
  11. temperatureto reflux for 3 h
  12. customconsumption of starting material but many side products
  13. customformed
  14. customSolvent was evaporated under reduced pressure
  15. customthe crude residue was purified by flash chromatography
  16. washeluting with cyclohexane

Sources & evidence

ORD record
ord-6e34d0ee06a447e09e92b723b0ae548a
Source dataset
uspto-grants-2011_08
Patent number
US07989449B2

Reaction notes

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