Acetic Acid → Ethyl 2-fluoro-4-nitrobenzoate

Temperature

90 °C

To a mixture of 2-fluoro-4-nitrotoluene (1.0 g, 6.4 mmol, Aldrich) and Na2Cr2O7 (2.74 g, 8.4 mmol) in 13.7 ml of HOAc was added slowly 6.83 ml of H2SO4. This mixture was slowly heated to 90° C. for 1 hour to give a greenish heterogeneous solution. The mixture was cooled to room temperature and diluted with ethyl acetate. The pH of the solution was adjusted to 4 with aqueous NaOH. The mixture was extracted with more ethyl acetate. The combined organic layers were washed with NaHCO3 (sat.), then brine and dried over Na2SO4. After filtration, the solution was concentrated to dryness which then was dissolved in 6 ml of SOCl2, and heated at 80° C. for 1 hour. The excess of SOCl2 was removed under reduced pressure and the residue was dissolved in 5 ml of CH2Cl2, 2 ml of EtOH and 2 ml of pyridine. The mixture was stirred at room temperature for 2 hours and concentrated to dryness. Ethyl 2-fluoro-4-nitrobenzoate was obtained as a white solid after column chromatography of the residue with ethyl acetate/hexane (1/9). This solid was then dissolved in 10 ml of ethyl acetate, and Pd/C (50 mg) was added. Hydrogenation converted ethyl 2-fluoro-4-nitrobenzoate into the title compound. 1H NMR δ 7.77 (t, J=8.4 Hz, 1H), 6.41 (dd, J1 =8.6, J2 =2.2 Hz, 1H), 6.33 (dd, J1 =13.0, J2 =2.2 Hz, 1H), 4.33 (q, J=7.1 Hz, 2H), 4.3 (b, 2H), 1.37 (t, J=7.1 Hz, 3H).

1. customto give a greenish heterogeneous solution
2. temperatureThe mixture was cooled to room temperature
3. extractionThe mixture was extracted with more ethyl acetate
4. washThe combined organic layers were washed with NaHCO3 (sat.)
5. dry with materialbrine and dried over Na2SO4
6. filtrationAfter filtration
7. concentrationthe solution was concentrated to dryness which
8. dissolutionthen was dissolved in 6 ml of SOCl2
9. temperatureheated at 80° C. for 1 hour
10. customThe excess of SOCl2 was removed under reduced pressure
11. dissolutionthe residue was dissolved in 5 ml of CH2Cl2
12. concentrationconcentrated to dryness

ORD record

ord-6a3621dc6f9f4b43a8c0ea14fe6a7004

Source dataset

uspto-grants-1997_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05663357