Methyl iodide → 5-Fluoro-2-nitroanisole

A solution of 5-fluoro-2-nitrophenol (10.0 g) in dry acetone (40 ml) under nitrogen was treated with potassium carbonate (8.9 g). The mixture formed a deep red coloured thick precipitate. Methyl iodide (5 ml, 11.4 g) was added slowly and the mixture stirred overnight and then at 60° C. for 3 hours. Further methyl iodide (3 ml, 6.84 g) was added and the mixture stirred at 60° C. for a further 3 hours. After this time the deep red colour had disappeared, and the mixture (now orange) was added to water (50 ml) and sodium hydroxide (2N, 40 ml), and extracted with dichloromethane (3×100 ml). The combined, dried extracts were concentrated in vacuo to give a yellow oil which upon cooling crystallised giving a pale yellow crystalline solid (4-fluoro-2-methoxy-1-nitrobenzene 10.88 g). A solution of this solid in ethanol:water (200 ml, 6:2) was added under vacuum to a prehydrogenated suspension of palladium (10% on carbon, 50% paste, 2.5 g) in ethanol:water (80 ml, 6:2). The suspension was stirred under an atmosphere of hydrogen for 2 hours, the suspension was filtered through Hyflo and the filtercake washed thoroughly with ethanol and water. The combined filtrates were concentrated in vacuo and the moist residue re-evaporated with ethanol. The purple oily residue was dissolved in dichloromethane (200 ml), dried, and concentrated in vacuo to give the title compound as a dark purple liquid. (7.73 g).

1. customThe mixture formed a deep red coloured thick precipitate
2. waitat 60° C. for 3 hours
3. stirringthe mixture stirred at 60° C. for a further 3 hours
4. extractionextracted with dichloromethane (3×100 ml)
5. customdried extracts
6. concentrationwere concentrated in vacuo
7. customto give a yellow oil which
8. temperatureupon cooling
9. customcrystallised

ORD record

ord-5f54400b8547420db4aabac5edf61775

Source dataset

uspto-grants-1996_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05510350