Sodium Cyanide → 2-Amino-6-(benzyloxy)-2-(fluoromethyl)hexanenitrile

HRID 1607762Notes

Reaction equation

HRID 1607762 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[Mg].[F:15][CH2:16][C:17]#[N:18].[C-:19]#[N:20].[Na+].[Cl-].[NH4+]>CCOCC.O>[F:15][CH2:16][C:17]([NH2:18])([CH2:2][CH2:3][CH2:4][CH2:5][O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:19]#[N:20]

Participants

8

Reactant 5

HCID 8929Sodium CyanideHCID 10420Acetonitrile, fluoro-HCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 13521262[(4-Chlorobutoxy)methyl]benzene

Product 1

HCID 145794862-Amino-6-(benzyloxy)-2-(fluoromethyl)hexanenitrileYield 62.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-40 °C

Procedure

Under an atmosphere of nitrogen, the Grignard reagent is prepared from 1-chloro-4-benzyloxybutane (39.7 g, 0.2 mol), magnesium turnings (10 g, 0.4 mol), and dry ether (400 ml). The Grignard solution is separated from the excess of magnesium, transferred to a 2 l flask, and cooled to -40° C. A solution of fluoroacetonitrile (10.6 g, 0.18 mol) in ether (100 ml) is added slowly, the temperature being maintained between -40° and -30° C. Stirring is continued for 30 minutes more at this temperature. The reaction mixture is then poured into a vigorously stirred solution of sodium cyanide (39 g) and ammonium chloride (59 g) in water (200 ml) containing some ice (200 g). The mixture is vigorously stirred and allowed to warm up to room temperature during one hour. The organic phase is separated and extracted with 1N HCl (2×250 ml). Basification with concentrated ammonia, extraction with ether, drying, and evaporation gives 2-fluoromethyl-2-amino-6-benzyloxyhexanenitrile as a brown oil (28.3 g).

Workup

  1. customThe Grignard solution is separated from the excess of magnesium
  2. customtransferred to a 2 l flask
  3. temperaturethe temperature being maintained between -40° and -30° C
  4. stirringThe mixture is vigorously stirred
  5. temperatureto warm up to room temperature during one hour
  6. customThe organic phase is separated
  7. extractionextracted with 1N HCl (2×250 ml)
  8. extractionBasification with concentrated ammonia, extraction with ether
  9. customdrying
  10. customevaporation

Sources & evidence

ORD record
ord-b534f1a16dad4e448aeaebde89385dfd
Source dataset
uspto-grants-1989_09
Patent number
US04866206

Reaction notes

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