1,2-Dibromoethane → Ethyl 4-(3,4-dichlorobenzyl)benzoate

HRID 2359339Notes

Reaction equation

HRID 2359339 reaction equation
[Cl-].[Li+].BrCCBr.Br[CH2:8][C:9]1[CH:19]=[CH:18][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][CH:10]=1.[Cl:20][C:21]1[CH:22]=[C:23](I)[CH:24]=[CH:25][C:26]=1[Cl:27].[Cl-].[NH4+]>C1COCC1.[Zn].CC(C1C=CC=C(C(C)C)C=1N1[CH-]N(C2C(C(C)C)=CC=CC=2C(C)C)CC1)C.C1C=NC=C(Cl)C=1.Cl[Pd]Cl.C[Si](Cl)(C)C>[Cl:20][C:21]1[CH:22]=[C:23]([CH:24]=[CH:25][C:26]=1[Cl:27])[CH2:8][C:9]1[CH:19]=[CH:18][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][CH:10]=1

Participants

10

Reactant 5

HCID 78391,2-DibromoethaneHCID 25517Ammonium ChlorideHCID 88591Benzene, 1,2-dichloro-4-iodo-HCID 433294Lithium ChlorideHCID 954261Ethyl 4-(bromomethyl)benzoate

Product 1

HCID 58046347Ethyl 4-(3,4-dichlorobenzyl)benzoateYield 53.9%

Reagents, catalysts & solvents 4

HCID 6397ChlorotrimethylsilaneCatalystHCID 23994ZincCatalyst2×HCID 588388791,3-Bis[2,6-di(propan-2-yl)phenyl]imidazolidin-2-ide;3-chloropyridine;dichloropalladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of zinc (404 mg, 6.17 mmol) and lithium chloride (261 mg, 6.17 mmol) under argon was warmed for 15 minutes using a hot air gun, allowed to cool and then anhydrous THF (20 mL) added. The zinc was activated by treatment with 1,2-dibromoethane (19 mg, 0.10 mmol) and TMSCl (2.2 mg, 0.02 mmol). To the resulting mixture at 25° C. was added ethyl 4-(bromomethyl)benzoate (500 mg, 2.06 mmol) and the mixture stirred for 15 minutes. A solution of 3,4-dichloro-iodobenzene (392 mg, 1.44 mmol) in anhydrous THF (5 mL) was added, followed by (1,3-bis(2,6-diisopropylphenyl)imidazolidene)(3-chloropyridyl)palladium(II) dichloride [PEPPSI™-SlP] (14 mg, 0.02 mmol) and the mixture stirred at 25° C. for 1 hour. Saturated ammonium chloride solution was added and the crude product extracted with ether. The ether extract was washed with brine, dried over Na2SO4 and the solvent evaporated in vacuo. The crude product was purified by silica gel column chromatography eluting with 7:3 hexane:ethyl acetate to afford the title compound (240 mg, 38%).

Workup

  1. temperaturewas warmed for 15 minutes
  2. temperatureto cool
  3. stirringthe mixture stirred at 25° C. for 1 hour
  4. extractionthe crude product extracted with ether
  5. extractionThe ether extract
  6. washwas washed with brine
  7. dry with materialdried over Na2SO4
  8. customthe solvent evaporated in vacuo
  9. customThe crude product was purified by silica gel column chromatography
  10. washeluting with 7:3 hexane

Sources & evidence

ORD record
ord-a67f175506ca4c13b9a89e3bc33e3cca
Source dataset
uspto-grants-2014_04
Patent number
US08685977B2

Reaction notes

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