Dimethyl Sulfate → Methyl o-toluate

o-Toluic acid (500 mg, 3.67 mmol), dimethyl sulfate (695 mg, 5.51 mmol), and K2CO3 (558 mg, 4.04 mmol) were placed in a round bottom flask and diluted with acetone (10 mL). After purging the resulting suspension with argon for 5 min, the mixture was heated to reflux for 2 h. The reaction mixture was cooled and concentrated under reduced pressure to remove acetone. After adding water to the mixture, the solution was extracted with ethyl acetate (×3). The combined extracts were washed with brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (Hex/EtOAc=9:1) to give 2-methylbenzoic acid methyl ester (Formula 4) (415 mg, 75%) as a white solid. Rf=0.5 (Hex:EtOAc=9:1); 1H NMR (300 MHz, CDCl3): δ 7.91 (dd, J=8.4 and 1.8 Hz, 1H), 7.40 (td, J=7.5 and 1.5 Hz, 1H), 7.24 (m, 2H), 3.89 (s, 3H), 2.60 (s, 3H).

1. customAfter purging the resulting suspension with argon for 5 min
2. temperaturethe mixture was heated
3. temperatureto reflux for 2 h
4. temperatureThe reaction mixture was cooled
5. concentrationconcentrated under reduced pressure
6. customto remove acetone
7. additionAfter adding water to the mixture
8. extractionthe solution was extracted with ethyl acetate (×3)
9. washThe combined extracts were washed with brine
10. dry with materialdried over anhydrous MgSO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe crude product was purified by flash chromatography on silica gel (Hex/EtOAc=9:1)

ORD record

ord-fd44be36765e4772a67336dee699bc30

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08034623B2