2-Bromotoluene → (+/-)-4'-[1-(Dimethylamino)ethyl]-2-methylbiphenyl

HRID 2255282Notes

Reaction equation

HRID 2255282 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH3:9].[CH3:10][N:11]([CH3:21])[CH:12]([C:14]1[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=1)[CH3:13]>O1CCCC1.C1(P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH3:10][N:11]([CH3:21])[CH:12]([C:14]1[CH:19]=[CH:18][C:17]([C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[CH3:9])=[CH:16][CH:15]=1)[CH3:13]

Participants

6

Reactant 3

HCID 72362-BromotolueneHCID 4192621-(4-bromophenyl)-N,N-dimethylethanamineHCID 5462224Magnesium

Product 1

HCID 19742087(+/-)-4'-[1-(Dimethylamino)ethyl]-2-methylbiphenylYield 97.2%

Reagents, catalysts & solvents 2

HCID 57646695Palladium;tetraphenyl-lambda5-phosphaneCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of the Grignard reagent prepared from 344 mg of magnesium and 2.27 g of 2-bromotoluene in 15 mL of tetrahydrofuran was added dropwise to a suspension of 2 g of (±)-1-dimethylamino-1-(4-bromophenyl)-ethane and 158 g of tetrakisphenylphosphine-palladium in 10 mL of tetrahydrofuran. The addition was effected at room temperature and under an argon atmosphere. After completion of the addition the mixture was heated to boiling for a further 5 hours and then evaporated under reduced pressure. The residue was then treated with 50 mL of ether and 50 mL of saturated ammonium chloride solution and the aqueous phase was separated. The aqueous phase was extracted twice with 50 mL of ether. The combined organic extracts were washed with saturated sodium chloride solution, dried over magnesium sulphate and evaporated. The residue was purified by chromatography on silica gel while eluting with methylene chloride/methanol 9:1. There was obtained 2.04 g (96%) of (±)-4'-[1-(dimethylamino)ethyl]-2-methylbiphenyl as a yellow oil.

Workup

  1. additionThe addition
  2. customwas effected at room temperature and under an argon atmosphere
  3. additionAfter completion of the addition the mixture
  4. temperaturewas heated
  5. customevaporated under reduced pressure
  6. additionThe residue was then treated with 50 mL of ether and 50 mL of saturated ammonium chloride solution
  7. customthe aqueous phase was separated
  8. extractionThe aqueous phase was extracted twice with 50 mL of ether
  9. washThe combined organic extracts were washed with saturated sodium chloride solution
  10. dry with materialdried over magnesium sulphate
  11. customevaporated
  12. customThe residue was purified by chromatography on silica gel
  13. washwhile eluting with methylene chloride/methanol 9:1

Sources & evidence

ORD record
ord-1d73da38141b4117990d537f6511a377
Source dataset
uspto-grants-1993_08
Patent number
US05239084

Reaction notes

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