Carbon Dioxide → 4-Fluoro-2-methylbenzoic acid

Temperature

0 °C

To a cooled (−78° C.) solution of 2-bromo-5-fluorotoluene (10.0 g, 52.9 mmol) in diethyl ether (100 mL) was added dropwise n-butyllithium (1.6 M in hexane, 21.2 mL, 52.9 mmol). The mixture was stirred for 5 min, and slowly warmed to 0° C. Dry ice (100 g, 2.27 mol) was slowly added to the mixture while stirring, and it was allowed to warm to rt over 16 h. The mixture was adjusted to pH=2, and extracted with ethyl acetate (3×20 mL). The organic phase was concentrated and the resulting yellow residue suspended in water (100 mL). The suspension was adjusted to pH=12 with 2 N NaOH, and washed with diethyl ether. The aqueous phase was then acidified to pH=2 with 2 N HCl, and extracted with diethyl ether (3×50 mL). The organic extract was washed with water, dried (MgSO4), and concentrated under reduced pressure to afford the product (5.0 mg, 61%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 2.53 (s, 3H), 7.06-7.17 (m, 2H), 7.87 (dd, 1H), 12.85 (s, 1H).

1. stirringwhile stirring
2. temperatureto warm to rt over 16 h
3. extractionextracted with ethyl acetate (3×20 mL)
4. concentrationThe organic phase was concentrated
5. washwashed with diethyl ether
6. extractionextracted with diethyl ether (3×50 mL)
7. extractionThe organic extract
8. washwas washed with water
9. dry with materialdried (MgSO4)
10. concentrationconcentrated under reduced pressure

ORD record

ord-d6888e8498134be3979dde964ec53759

Source dataset

uspto-grants-2007_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07265144B2