Sodium Chloride → 2-Fluoromethyl-2-amino-5-benzyloxypentanenitrile

HRID 1995564Notes

Reaction equation

HRID 1995564 reaction equation
[Mg].CI.Cl[CH2:5][CH2:6][CH2:7][O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[F:16][CH2:17][C:18]#[N:19].[C-:20]#[N:21].[Na+].[Cl-].[NH4+].[Cl-].[Na+]>CCOCC.O>[F:16][CH2:17][C:18]([NH2:19])([CH2:5][CH2:6][CH2:7][O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:20]#[N:21]

Participants

10

Reactant 7

HCID 5234Sodium ChlorideHCID 6328Methyl iodideHCID 8929Sodium CyanideHCID 10420Acetonitrile, fluoro-HCID 25517Ammonium ChlorideHCID 221505((3-Chloropropoxy)methyl)benzeneHCID 5462224Magnesium

Product 1

HCID 147716532-Fluoromethyl-2-amino-5-benzyloxypentanenitrileYield 55.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent4×

Conditions

Temperature
-40 °C

Procedure

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 (1.1 l) 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 mol) 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 1 N HCl (2×750 ml) and re-extracted with ether (2×750 ml) after basification with concentrated ammonia. Drying (Na2SO4) and evaporation gives the title compound as a brown oil (74.8 g).

Workup

  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 1 N HCl (2×750 ml)
  9. extractionre-extracted with ether (2×750 ml) after basification with concentrated ammonia
  10. customDrying
  11. custom(Na2SO4) and evaporation

Sources & evidence

ORD record
ord-ce5d2198074e4cefb9e8a1cdcba3c807
Source dataset
uspto-grants-1983_09
Patent number
US04405530

Reaction notes

Loading…