Carbon Dioxide → 4-Fluoro-2-methylbenzoic acid

Temperature

55 °C

To a flask fit with a reflux condenser and addition funnel was added magnesium (2.6 g, 106 mmol) and tetrahydrofuran (10 mL). A solution of 2-bromo-5-fluorotoluene (1.0 g, 5.3 mmol) in tetrahydrofuran (2 mL) and dibromoethane (0.04 mL) was added. The solution was warmed gently in a 55° C. oil bath until a vigorous reflux began. A solution of 2-bromo-5-fluorotoluene (9.0 g, 48 mmol) in tetrahydrofuran (18 mL) was added dropwise to maintain a gentle reflux. After addition was complete, the reaction mixture was heated in a 55° C. oil bath for 1 h. The reaction mixture was allowed to cool to room temperature and poured onto crushed dry ice (50 mL). The excess dry ice was allowed to sublime. The solution was partitioned between ethyl acetate (100 mL) and 3% HCl (50 mL). The organic layer was washed with brine, dried over magnesium sulfate, and the solvent was removed in vacuo. to afford the title compound (8.3 g) in quantitative yield. Rf=0.34 (silica gel, 5% isopropanol/dichloromethane).

1. additionTo a flask fit with a reflux condenser and addition funnel
2. temperaturea vigorous reflux
3. temperatureto maintain a gentle reflux
4. additionAfter addition
5. temperaturethe reaction mixture was heated in a 55° C. oil bath for 1 h
6. temperatureto cool to room temperature
7. additionpoured
8. customThe solution was partitioned between ethyl acetate (100 mL) and 3% HCl (50 mL)
9. washThe organic layer was washed with brine
10. dry with materialdried over magnesium sulfate
11. customthe solvent was removed in vacuo

ORD record

ord-63d22a5d92a24c768d15e221ecfe9d7c

Source dataset

uspto-grants-2002_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06342504B1