Reaction #7065

Reaction equation

4-bromo-3-chlorotoluene

1,3-bis(diphenylphosphino)propane

triethylamine

methanol

dimethylformamide

→

methyl 2-chloro-4-methylbenzoate

Yield 28.0%

Conditions

Workup

1. 1
   OtherThe reaction vessel is evacuated
2. 2
   Otherpurged three times with carbon monoxide gas
3. 3
   workup.ADDITIONA balloon filled with carbon monoxide gas
4. 4
   Temperatureto maintain the carbon monoxide atmosphere
5. 5
   WashThe mixture is washed with water
6. 6
   Extractionextracted with hexanes (2×50 mL)
7. 7
   DryingThe combined organic layers are dried over sodium sulfate
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated
10. 10
    Otherchromatographed with 0–3% ethyl acetate in hexanes

Procedure

To 4-bromo-3-chlorotoluene (4.97 g, 24.2 mmol) in dimethylformamide (25 mL) is added palladium acetate (0.54 g, 2.42 mmol), 1,3-bis(diphenylphosphino)propane (0.998 g, 2.42 mmol), triethylamine (12.5 mL) and methanol (12.5 mL). The reaction vessel is evacuated and purged three times with carbon monoxide gas. A balloon filled with carbon monoxide gas is used to maintain the carbon monoxide atmosphere. The reaction mixture is heated at 80° C. for 8 hr. The mixture is washed with water and extracted with hexanes (2×50 mL). The combined organic layers are dried over sodium sulfate, filtered, concentrated, and chromatographed with 0–3% ethyl acetate in hexanes. 1.24 g (28%) of methyl 2-chloro-4-methylbenzoate is isolated as a colorless oil.

Source