Water → HCID 57825242, compound

HRID 1668719Notes

Reaction equation

HRID 1668719 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]([Cl:15])[CH:8]=1.[CH3:16][C:17]([C:19]1[CH:24]=[CH:23][C:22]([F:25])=[C:21]([Br:26])[CH:20]=1)=O.O>O1CCCC1>[Br:26][C:21]1[C:22]([F:25])=[CH:23][CH:24]=[C:19]([C:17]([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]([Cl:15])[CH:8]=2)=[CH2:16])[CH:20]=1

Participants

6

Reactant 4

HCID 962WaterHCID 705081-(3-Bromo-4-fluorophenyl)ethan-1-oneHCID 30165374-Bromo-2-chloroanisoleHCID 178418339Butyllithium

Product 1

HCID 57825242HCID 57825242, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of n-butyllithium (1.6 M solution in hexane, 20 mL, 1.1 eq) was added dropwise to a solution of 4-bromo-2-chloro-1-methoxy-benzene (6 g, 27 mmol, 1 eq) in tetrahydrofuran (25 mL) at −78° C. After stirring 30 min 3-bromo-4-fluoroacetophenone (5.8 g, 27 mmol, 1 eq) in tetrahydrofuran (25 mL) was added dropwise. The mixture was allowed to warm up to room temperature and stirred for 2 h, then treated with water (10 mL), extracted with ethyl acetate, dried (sodium sulfate) and concentrated in vacuo. The crude was dissolved in acetic acid (80 mL) and concentrated sulfuric acid (17 mL) was added. The mixture was warmed to 75° C. for 30 min, cooled at room temperature and neutralized with 1 N NaOH. The aqueous phase was extracted with dichloromethane (3×100 mL), dried (sodium sulfate) the solvent was removed under reduced pressure. The residue was purified by column chromatography (cyclohexane) to afford the title compound as a colourless oil (3.2 g, 36%);

Workup

  1. additionwas added dropwise
  2. extractionextracted with ethyl acetate
  3. dry with materialdried (sodium sulfate)
  4. concentrationconcentrated in vacuo
  5. dissolutionThe crude was dissolved in acetic acid (80 mL)
  6. additionconcentrated sulfuric acid (17 mL) was added
  7. temperatureThe mixture was warmed to 75° C. for 30 min
  8. temperaturecooled at room temperature and neutralized with 1 N NaOH
  9. extractionThe aqueous phase was extracted with dichloromethane (3×100 mL)
  10. dry with materialdried (sodium sulfate) the solvent
  11. customwas removed under reduced pressure
  12. customThe residue was purified by column chromatography (cyclohexane)

Sources & evidence

ORD record
ord-654e0146cad541ba86fd49e9dce65add
Source dataset
uspto-grants-2011_08
Patent number
US07989449B2

Reaction notes

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