Nitric Acid → 2-Fluoro-5-methoxyaniline

To a stirred mixture of 2,6-dibromo-4-fluoroanisole (52.5 g, 0.185 mol) in 98% sulfuric acid (152 mL) at 15° C. was added, dropwise over 0.5 h, a solution of nitric acid (9.2 mL) and sulfuric acid (152 mL) with external ice-bath cooling. The mixture was stirred at 20° C. over 4 h, then was poured into ice water (1 kg) and extracted with dichloromethane (3×150 mL). The combined extracts were dried (Na2SO4) and evaporated in vacuo to give a brown oil. Chromatography on silica with 1-50% ether in hexane gradient elution gave an off-white solid, a solution of which in ethanol (250 mL) was hydrogenated at 20° C. and 4 bar over 10% palladium on carbon (3.5 g) for 18 h. Catalyst was removed by filtration and the filtrate was evaporated in vacuo to give a residue which was partitioned between saturated aqueous NaHCO3 (300 mL) and dichloromethane (3×100 mL). The combined organic extracts were dried (Na2SO4) and evaporated in vacuo to give an oil. Chromatography on silica with 20-50% ether in hexane gradient elution gave the title compound (15.3 g, 59%) as an oil.

1. additionwas added, dropwise over 0.5 h
2. extractionextracted with dichloromethane (3×150 mL)
3. dry with materialThe combined extracts were dried (Na2SO4)
4. customevaporated in vacuo
5. customto give a brown oil
6. washChromatography on silica with 1-50% ether in hexane gradient elution
7. customgave an off-white solid
8. customwas hydrogenated at 20° C.
9. customCatalyst was removed by filtration
10. customthe filtrate was evaporated in vacuo
11. customto give a residue which
12. customwas partitioned between saturated aqueous NaHCO3 (300 mL) and dichloromethane (3×100 mL)
13. dry with materialThe combined organic extracts were dried (Na2SO4)
14. customevaporated in vacuo
15. customto give an oil
16. washChromatography on silica with 20-50% ether in hexane gradient elution

ORDレコード

ord-1697e1e3b3cd43a683c5d31a7f773282

出典データセット

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06939871B2