Ammonia → 2-Amino-2-(4-chloro-3-fluorophenyl)acetonitrile

To a solution of 25.0 g (158 mmol) 4-chloro-3-fluorobenzaldehyde in 130 ml methanol and 175 ml methanol saturated with ammonia were added 54.9 ml (52.7 g, 185 mmol) tetraisopropyl orthotitanate and the mixture stirred at ambient temperature for 1.5 hours. Then 20.35 ml (16.14 g, 163 mmol) trimethylsilyl cyanide were added drop-wise and the resulting mixture stirred at ambient temperature for further 2 hours. The reaction mixture was poured onto 1500 ml iced water and extracted with ethyl acetate. The combined organic phases were washed with brine, dried over Na2SO4 and evaporated. The crude product was purified by flash-chromatography on silica gel with a gradient of heptane and 0 to 50% ethyl acetate. rac-Amino-(4-chloro-3-fluoro-phenyl)-acetonitrile was obtained as orange oil: MS (ISN): 183.2 (M−H)−.

1. stirringthe resulting mixture stirred at ambient temperature for further 2 hours
2. extractionextracted with ethyl acetate
3. washThe combined organic phases were washed with brine
4. dry with materialdried over Na2SO4
5. customevaporated
6. customThe crude product was purified by flash-chromatography on silica gel with a gradient of heptane and 0 to 50% ethyl acetate

ORD-Eintrag

ord-c58137df8a8b447993670e0bde63c0ca

Quelldatensatz

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08367838B2