Ethanol → 4-Cyclopropyl-2-fluoroaniline

A mixture of 4-cyclopropyl-2-fluoro-1-nitrobenzene (3.36 g, 18.55 mmol), powdered iron (4.35 g, 77.9 mmol), and 2M ammonium chloride in water (19.8 mL) and 3:2:1 v/v EtOH:THF:H2O (86 mL) was stirred at reflux under N2 for 17 h. The reaction mixture was cooled to RT and filtered through a pad of Celite. The Celite pad was rinsed well with ethyl acetate (˜50 mL). Saturated aqueous NaHCO3 solution was slowly added to the filtrate to neutralize the reaction mixture. The reaction mixture was extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude residue was purified via flash column chromatography eluted with 0 to 75% ethyl acetate/hexane to give 2.80 g (99%) of an orange oil, which solidified at 20° C. 1H NMR (400 MHz, CDCl3) δ 6.75-6.63 (m, 3H), 3.57 (s, 2H), 1.87-1.72 (m, 1H), 0.93-0.83 (m, 2H), 0.64-0.51 (m, 2H); MS (ESI) m/z: 152.3 [M+H]+.

1. temperatureat reflux under N2 for 17 h
2. filtrationfiltered through a pad of Celite
3. washThe Celite pad was rinsed well with ethyl acetate (˜50 mL)
4. additionSaturated aqueous NaHCO3 solution was slowly added to the filtrate
5. extractionThe reaction mixture was extracted with ethyl acetate (3×200 mL)
6. washThe combined organic layers were washed with water and brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe crude residue was purified via flash column chromatography
11. washeluted with 0 to 75% ethyl acetate/hexane

ORD record

ord-04fd3368954e4647bf5ae79def2f3b4d

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08436001B2