2-Methoxyethanol → 4-Fluoro-3-(2-methoxyethoxy)aniline

1-Fluoro-2-(2-methoxyethoxy)-4-nitrobenzene. Diisopropyl azodicarboxylate (1.356 mL, 7.00 mmol) was added dropwise to a stirred solution of 2-fluoro-5-nitrophenol (1.00 g, 6.37 mmol), triphenylphosphine (1.837 g, 7.00 mmol), and 2-methoxyethanol (0.533 g, 7.00 mmol) in tetrahydrofuran (10 mL) cooled with a water bath. The resulting dark red mixture was stirred at room temperature under nitrogen for 1.5 h. The resulting mixture was purified using flash chromatography (Biotage) (0-30% ethyl acetate in hexane). Fractions containing the desired product were combined and washed twice with water and once with brine. The organics were dried over magnesium sulfate, filtered, and concentrated on a rotary evaporator nearly to dryness. The residue was diluted with cold hexane. Solids were collected by vacuum filtration, washed with cold hexane, and dried under high vacuum to give the desired product (0.865 g, 4.02 mmol, 63% yield) as slightly yellow needles. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 8.01 (dd, J=2.73, 7.42 Hz, 1H), 7.91 (ddd, J=2.73, 3.90, 8.98 Hz, 1H), 7.54 (dd, J=8.98, 10.93 Hz, 1H), 4.31-4.39 (m, 2H), 3.67-3.76 (m, 2H), 3.32 (s, 3H); MS (ESI) m/z 216.3 [M+1]+.

1. temperaturecooled with a water bath
2. customThe resulting mixture was purified
3. additionFractions containing the desired product
4. washwashed twice with water and once with brine
5. dry with materialThe organics were dried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated on a rotary evaporator nearly to dryness
8. additionThe residue was diluted with cold hexane
9. filtrationSolids were collected by vacuum filtration
10. washwashed with cold hexane
11. customdried under high vacuum

ORD record

ord-c8affc16c7fe433d9613443c820ede0d

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08299056B2