Ethyl 3-bromo-4-chlorobenzoate → 4-Chloro-3-(1-methylethyl)-benzoic acid ethyl ester

HRID 2410080Notes

Reaction equation

HRID 2410080 reaction equation
[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[CH:9][C:8]([Cl:11])=[C:7](Br)[CH:6]=1)[CH3:2].[CH:14]([Zn]C(C)C)([CH3:16])[CH3:15]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[CH:9][C:8]([Cl:11])=[C:7]([CH:14]([CH3:16])[CH3:15])[CH:6]=1)[CH3:2]

Participants

5

Reactant 2

HCID 12594300Ethyl 3-bromo-4-chlorobenzoateHCID 178461828HCID 178461828, compound

Product 1

HCID 577427574-Chloro-3-(1-methylethyl)-benzoic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

3-Bromo-4-chlorobenzoic acid ethyl ester (1.05 g, 3.99 mmol) was added in one portion to a solution of diisopropylzinc (10.0 mmol, 1M toluene, Aldrich) in 10 mL of 1,4-dioxane followed by addition of Pd(dppf)2Cl2 (4.0 mmol). The mixture was heated to reflux 3 hours, cooled to ambient temperature and stirred overnight. The mixture was quenched with 1N aqueous HCl, diluted with ethyl acetate, and filtered through celite. The separated organic layer was washed sequentially with 1N aqueous HCl, brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by chromatography eluting with 4% ethyl acetate/hexanes to provide the title compound. 1H NMR (DMSO-d6) δ 7.92 (d, 1H), 7.78 (dd, 1H), 7.58 (d, 1H), 4.32 (q, 2H), 3.35 (sept, 1H), 1.32 (t, 3H), 1.24 (d, 6H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux 3 hours
  3. customThe mixture was quenched with 1N aqueous HCl
  4. additiondiluted with ethyl acetate
  5. filtrationfiltered through celite
  6. washThe separated organic layer was washed sequentially with 1N aqueous HCl, brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by chromatography
  11. washeluting with 4% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-f8d78d4d1ec44af9942a3d93c368146f
Source dataset
uspto-grants-2014_08
Patent number
US08815930B2

Reaction notes

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