Hydrochloric Acid → (1R,2S)-2-(3,4-Difluorophenyl)cyclopropanamine

A solution of (1R,2R)-2-(3,4-difluorophenyl)cyclopropanecarboxylic acid (8.0 g, 40.40 mmol, 1.00 equiv.), diphenylphosphoryl azide (11.2 g, 40.73 mmol, 1.00 equiv.), triethylamine (6.2 g, 61.39 mmol, 1.50 equiv.) in toluene (60 mL) was heated at reflux for about 1 hour and then refluxing 6N hydrogen chloride was added. The mixture was kept at reflux for 16 hours, and then cooled to ambient temperature. The resulting mixture was concentrated in vacuo, and the resulting residue was dissolved in water/ether (1:1) 200 mL). Following standard extractive workup with ether (3×100 mL), the resulting residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether (1:4˜1:0)) to give the title product as a light-brown solid (6.2 g; yield=91%). 1H NMR (300 MHz, CDCl3) δ: 6.98-7.07 (m, 1H), 6.72-6.81 (m, 2H), 2.40 (m, 1H), 1.82-1.87 (m, 1H), 1.05-1.11 (m, 1H), 0.85-0.96 (m, 1H).

1. temperatureat reflux for about 1 hour
2. additionwas added
3. temperatureat reflux for 16 hours
4. concentrationThe resulting mixture was concentrated in vacuo
5. dissolutionthe resulting residue was dissolved in water/ether (1:1) 200 mL)
6. customthe resulting residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether (1:4˜1:0))

ORD-Eintrag

ord-b230c3126e4c4ac595b72a00ab264027

Quelldatensatz

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09255104B2