Nitric Acid → 2,4-Difluoro-5-nitrophenol

Temperature

15 °C

To a solution of ethyl 2,4-difluorophenoxycarboxylate (3.27 g, 16.2 mmol) in concentrated H2SO4 (11 mL) at 0° C. was added fuming HNO3 (1.1 mL) dropwise, maintaining the internal temperature between 10 to 20° C. After stirring for 1 h, the mixture was poured over ice water (100 mL) and extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine (2×40 mL), dried over MgSO4, and concentrated in vacuo. The residue was dissolved in MeOH (50 mL), and sodium bicarbonate (2.72 g, 32.3 mmol) was added. The resultant mixture was stirred at room temperature for 64 h and the solid was filtered. The filtrate was concentrated and the residue was taken up in H2O (100 mL). The pH was adjusted to 5 with the addition of conc. HCl, and the mixture was extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine (2×40 mL), dried over MgSO4, and evaporated under reduced pressure to give 2,4-difluoro-5-nitrophenol as a yellow solid (2.35 g, 13.4 mmol; 83% yield). 1H-NMR (DMSO-d6) δ 10.88 (s, 1H), 7.70 to 7.61 (m, 2H),

1. extractionextracted with EtOAc (3×50 mL)
2. washThe combined organic layers were washed with brine (2×40 mL)
3. dry with materialdried over MgSO4
4. concentrationconcentrated in vacuo
5. dissolutionThe residue was dissolved in MeOH (50 mL)
6. filtrationthe solid was filtered
7. concentrationThe filtrate was concentrated
8. additionThe pH was adjusted to 5 with the addition of conc. HCl
9. extractionthe mixture was extracted with EtOAc (3×50 mL)
10. washThe combined organic layers were washed with brine (2×40 mL)
11. dry with materialdried over MgSO4
12. customevaporated under reduced pressure

ORD record

ord-3e7fdce486ac42a89e328c37753e1226

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08076488B2