Bromide ion → 4-[1-(3-Bromo-phenyl)-vinyl]-1-methoxy-2-trifluoromethyl-benzene

HRID 1668723Notes

Reaction equation

HRID 1668723 reaction equation
[Mg].Br[C:3]1[CH:4]=[CH:5][C:6]([O:13][CH3:14])=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[Br-].[CH3:16][C:17]([C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([Br:25])[CH:20]=1)=O>O1CCCC1.BrCCBr>[Br:25][C:21]1[CH:20]=[C:19]([C:17]([C:3]2[CH:4]=[CH:5][C:6]([O:13][CH3:14])=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=2)=[CH2:16])[CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 259Bromide ionHCID 165023'-BromoacetophenoneHCID 27753044-Bromo-1-methoxy-2-(trifluoromethyl)benzeneHCID 5462224Magnesium

Product 1

HCID 578251474-[1-(3-Bromo-phenyl)-vinyl]-1-methoxy-2-trifluoromethyl-benzene

Reagents, catalysts & solvents 2

HCID 78391,2-DibromoethaneSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a suspension of magnesium turnings (565 mg, 23.5 mmol, 1.2 eq) in 5 mL of dry tetrahydrofuran, 0.1 mL of 1,2-dibromoethane were added followed by 5 mL of a tetrahydrofuran solution of 5-bromo-2-methoxy-benzotrifluoride (5.0 g, 19.6 mmol, 1.0 eq in 30 mL tetrahydrofuran). The resulting mixture was gently heated to initiate the reaction. The remaining solution of bromide was added dropwise at such a rate that the reaction could reflux without external heating. After the addition the reaction mixture was heated at reflux for further 2 hours. The mixture was cooled to 0° C. and a solution of 3-bromoacetophenone (3.9 g, 19.6 mmol, 1.0 eq) in tetrahydrofuran (30 mL) was added dropwise. After 2 hours LC-MS showed complete conversion to the desired product. 50 mL of water were added followed by 25 mL of 1 M aqueous HCl. The organic fraction was washed with brine, dried over sodium sulfate and concentrated to give a yellow oil. The oil was dissolved in toluene (50 mL) and a few crystals of p-toluenesulfonic acid were added. The solution was heated to reflux for 2 hours in a flask equipped with a Dean-Stark apparatus. After this time, the mixture was cooled to room temperature, concentrated and the crude purified by flash chromatography eluting with cyclohexane/ethyl acetate (100:0 to 95:5). 5.1 g of clean product was obtained as colorless liquid (yield: 73%).

Workup

  1. additionwere added
  2. temperatureThe resulting mixture was gently heated
  3. customthe reaction
  4. customthat the reaction
  5. temperaturecould reflux without external heating
  6. additionAfter the addition the reaction mixture
  7. temperaturewas heated
  8. temperatureat reflux for further 2 hours

Sources & evidence

ORD record
ord-3b94ee26798c4dbe96178c46c8012468
Source dataset
uspto-grants-2011_08
Patent number
US07989449B2

Reaction notes

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