Methanol → Methyl 4-bromo-2-methylbenzoate

To a solution of 4-bromo-2-methylbenzoic acid (5.11 g, 23.8 mmol, 1.0 equiv) in methanol (25 mL) was added dropwise sulfuric acid (2.0 mL) over about 3 minutes (mildly exothermic). The resulting mixture was refluxed for 4 hours. After cooling to room temperature, the reaction mixture was carefully quenched into saturated aqueous NaHCO3 (100 mL) (note—significant gas evolution) and extracted with dichloromethane (200 mL×1 then 50 mL×1). The combined organic phases were washed with a mixture of brine/saturated NaHCO3 (9:1) (50 mL), dried (Na2SO4), and concentrated under reduced pressure to yield the title compound as a colorless oil (5.28 g, 97%). 1H NMR (400 MHz, CDCl3): δ 7.78 (d, J=8.0 Hz, 1H), 7.42 (d, J=1.6 Hz, 1H), 7.38 (dd, J=1.6 Hz, 1H), 3.89 (s, 3H), 2.58 (s, 3H).

1. temperatureThe resulting mixture was refluxed for 4 hours
2. customthe reaction mixture was carefully quenched into saturated aqueous NaHCO3 (100 mL) (note—significant gas evolution)
3. extractionextracted with dichloromethane (200 mL×1
4. washThe combined organic phases were washed with a mixture of brine/saturated NaHCO3 (9:1) (50 mL)
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated under reduced pressure

ORD record

ord-d4103063c12a4dc0aa887e2884900a28

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428502B2