Methyl iodide → Methyl 4-fluoro-2-methylbenzoate

Temperature

70 °C

To a solution of 4-fluoro-2-methylbenzoic acid (4.0 g, 26.0 mmol) in THF (30 mL) in a pressure vessel was added cesium carbonate (8.45 mg, 26.0 mmol) and iodomethane (2.0 M in tert-butyl methyl ether, 13.0 mL, 26.0 mmol). The vessel was sealed and the reaction was stirred at 70° C. for 16 h. After cooling to rt, the reaction was quenched with saturated sodium bicarbonate (10 mL) and water (50 mL). The aqueous layer was extracted with dichloromethane (3×50 mL), and then the organic phase was dried (Na2SO4) and concentrated under reduced pressure to give the crude product. This material was triturated with acetone and hexanes to afford pure product (3.8 g, 87%) as a white solid. 1H NMR (400 MHz, acetone-d6) δ 2.60 (s, 3H), 3.86 (s, 3H), 7.05-7.12 (m, 2H), 7.96 (s, 1H); ES-MS m/z 168.2 (MH+); HPLC RT (min) 3.20.

1. customThe vessel was sealed
2. temperatureAfter cooling to rt
3. customthe reaction was quenched with saturated sodium bicarbonate (10 mL) and water (50 mL)
4. extractionThe aqueous layer was extracted with dichloromethane (3×50 mL)
5. dry with materialthe organic phase was dried (Na2SO4)
6. concentrationconcentrated under reduced pressure
7. customto give the crude product
8. customThis material was triturated with acetone and hexanes

ORD record

ord-2b4c01148fec48f492cf07e452bc0da8

Source dataset

uspto-grants-2007_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07265144B2