1,2-Difluoro-3-nitrobenzene → 2-fluoro-N-(4-methoxybutyl)-6-nitroaniline

Temperature

60 °C

To a solution of 1,2-difluoro-3-nitrobenzene (5.15 g) and 4-methoxybutan-1-amine hydrochloride (5.42 g) in acetonitrile (100 ml) was added diisopropylethylamine (17 μl), and the mixture was stirred at 60° C. for 12 hr. 4-Methoxybutan-1-amine hydrochloride (1.00 g) was further added, and the mixture was stirred at 70° C. for 5 hr. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogen carbonate was added, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with hexane-ethyl acetate-hexane (3:7) was concentrated under reduced pressure to give the object product (7.70 g).

1. stirringthe mixture was stirred at 70° C. for 5 hr
2. concentrationThe reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogen carbonate
3. additionwas added
4. extractionthe mixture was extracted with ethyl acetate
5. dry with materialThe extract was dried over anhydrous magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. washa fraction eluted with hexane-ethyl acetate-hexane (3:7)
8. concentrationwas concentrated under reduced pressure

ORD record

ord-b63ebd0c21054cb6a16e7eef8d45aa3b

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09045436B2