Ethyl 3-bromo-4-chlorobenzoate → 4-Chloro-3-(3,3-dimethylbutyl)benzoic acid ethyl ester

HRID 499943Notes

Reaction equation

HRID 499943 reaction equation
[CH3:1][C:2]([CH3:8])([CH3:7])[CH2:3][CH2:4][Mg]Cl.[CH2:9]([O:11][C:12](=[O:21])[C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[C:15](Br)[CH:14]=1)[CH3:10]>O1CCOCC1.C(OCC)C.[Cl-].[Cl-].[Zn+2].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]>[CH2:9]([O:11][C:12](=[O:21])[C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([CH2:4][CH2:3][C:2]([CH3:8])([CH3:7])[CH3:1])[CH:14]=1)[CH3:10]

Participants

7

Reactant 2

HCID 12594300Ethyl 3-bromo-4-chlorobenzoateHCID 178444610HCID 178444610, compound

Product 1

HCID 685074754-Chloro-3-(3,3-dimethylbutyl)benzoic acid ethyl ester

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Procedure

3,3-dimethyl-1-butylmagnesium chloride (8.00 mmol, 0.5 M THF, Platte Valley Scientific) was added dropwise to a solution of ZnCl2 (4.00 mmol, IM diethyl ether, Aldrich) in 1,4-dioxane (15 mL) at ambient temperature. The mixture was stirred 30 minutes followed by addition of 3-bromo-4-chlorobenzoic acid ethyl ester (1.05 g, 3.99 mmol) and Pd(dppf)2Cl2 (131 mg, 0.160 mmol). The mixture was heated to reflux for 30 minutes, cooled to ambient temperature, diluted with diethyl ether and quenched with H2O. The mixture was filtered through celite and the filtrate was washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. Flash chromatography eluting with 5% to 15% ethyl acetate/hexanes provided the title compound. 1H NMR (DMSO-d6) δ 7.89 (d, 1H), 7.78 (dd, 1H), 7.56 (d, 1H), 4.32 (q, 2H), 2.73 (m, 2H), 1.41 (m, 2H), 1.32 (t, 3H), 0.97 (s, 9H); MS (DCI+) m/z 286 (M+NH4)+, 269 (M+H)+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 30 minutes
  3. customquenched with H2O
  4. filtrationThe mixture was filtered through celite
  5. washthe filtrate was washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. washFlash chromatography eluting with 5% to 15% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-3336679174de47a39da913e9c74ad409
Source dataset
uspto-grants-2010_08
Patent number
US07767705B2

Reaction notes

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