反应详情

温度

-40 °C

To magnesium turnings (30.6 g, 1.26 mol), suspended in dry ether (150 ml) is added methyl iodide (~ 0.5 ml) and then a solution of 1-chloro-3-benzyloxypropane (116 g, 0.63 mol) in ether (1.1l) at such a rate that gentle reflux is maintained. This procedure is performed under nitrogen. After the mixture is heated for 1 more hour under reflux, titration indicates Grignard formation to be complete. The solution is separated from the excess of magnesium (glass wool), transfered to a 6 l flask and, again under nitrogen, cooled to -40° C. Fluoroacetonitrile (33.48 g, 0.57 mmol) in ether (300 ml) is added slowly. The mixture is then kept at -40° C. for another 1/2 hour and is poured into a mixture of sodium cyanide (123 g), ammonium chloride (186 g), ice (600 g), and water (650 ml). The mixture is stirred vigorously and allowed to warm up to room temperature during 1 hour. Ether is added, the aqueous phase is saturated with sodium chloride, and the organic layer is separated. The aminonitrile is extracted with 1N HCl (2×750 ml) and re-extracted with ether (2×750 ml) after basification with concentrated ammonia. Drying (Na2SO4) and evaporation gives 2-fluoromethyl-2-amino-5-benzyloxypentanenitrile as a brown oil (74.8 g).

1. temperatureis maintained
2. temperatureAfter the mixture is heated for 1 more hour
3. temperatureunder reflux
4. customThe solution is separated from the excess of magnesium (glass wool)
5. customtransfered to a 6 l flask and, again under nitrogen
6. temperatureto warm up to room temperature during 1 hour
7. customthe organic layer is separated
8. extractionThe aminonitrile is extracted with 1N HCl (2×750 ml)
9. extractionre-extracted with ether (2×750 ml) after basification with concentrated ammonia
10. customDrying
11. custom(Na2SO4) and evaporation