Methanol → Methyl 2-chloro-4-methylbenzoate

Temperature

80 °C

To 4-bromo-3-chlorotoluene (4.97 g, 24.2 mmol) in DMF (25 mL) is added Pd(OAc)2 (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. After cooling H2O (50 mL) is added. The mixture is extracted with hexanes (2×50 mL). The combined organic layers are dried over Na2SO4, filtered, concentrated and chromatographed with 0–3% EtOAc in hexanes. 1.24 g (28%) of methyl 2-chloro-4-methylbenzoate is isolated as a colorless oil. EIMS m/e 184 (M+; 35Cl) and 186 (M+; 37Cl).

1. customThe reaction vessel is evacuated
2. custompurged three times with carbon monoxide gas
3. additionA balloon filled with carbon monoxide gas
4. temperatureto maintain the carbon monoxide atmosphere
5. temperatureAfter cooling H2O (50 mL)
6. additionis added
7. extractionThe mixture is extracted with hexanes (2×50 mL)
8. dry with materialThe combined organic layers are dried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customchromatographed with 0–3% EtOAc in hexanes

ORD record

ord-722eefee9f754a47a0574d530b790364

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07183320B2