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

HRID 1607755Notes

Reaction equation

HRID 1607755 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 55,538%

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 (1.110 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), transferred 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).

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. customtransferred 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

Sources & evidence

ORD record
ord-95beef08c28a41b6b53159491d51a93a
Source dataset
uspto-grants-1989_09
Patent number
US04866206

Reaction notes

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