Tetrahydrofuran → 2-Amino-5-(benzyloxy)-2-(difluoromethyl)pentanenitrile

HRID 1995576

Reaction equation

HRID 1995576 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[Mg:13].[F:14][CH:15]([F:18])[C:16]#[N:17].C1COCC1.[C-:24]#[N:25].[Na+].[Cl-:27].[NH4+]>CCOCC.O>[CH2:6]([O:5][CH2:4][CH2:3][CH2:2][Mg:13][Cl:27])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[F:14][CH:15]([F:18])[C:16]([NH2:17])([CH2:2][CH2:3][CH2:4][O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:24]#[N:25]

Participants

10

Reactant 6

HCID 8028TetrahydrofuranHCID 8929Sodium CyanideHCID 25517Ammonium ChlorideHCID 120219Acetonitrile, difluoro-HCID 221505((3-Chloropropoxy)methyl)benzeneHCID 5462224Magnesium

Product 2

HCID 204820032-Amino-5-(benzyloxy)-2-(difluoromethyl)pentanenitrileHCID 178479006HCID 178479006, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
-40 °C

Procedure

Under an atmosphere of nitrogen, 3-benzyloxypropyl-magnesium chloride is prepared from 1-chloro-3-benzyloxypropane (2.42 g, 13 mmol) in dry ether (13 ml) and magnesium turnings (660 mg, 26 mmol). The Grignard solution is separated from the excess of magnesium, cooled to -40° C., and a 10% solution of difluoroacetonitrile in dry THF (10 ml, 13 mmol) is added dropwise, maintaining the temperature at -40° C. After stirring at this temperature, for 30 minutes, the mixture is poured into a cold (0° C.) solution of sodium cyanide (1.27 g) and ammonium chloride (2.10 g) in water (40 ml). The mixture is stirred vigorously for 1 hour; during that time the reaction is allowed to warm up to room temperature. The organic phase is separated and extracted with 2 N HCl. Basification with concentrated ammonia (pH ~9-10), extraction with ether, drying, and evaporation gives the title compound as an oil (1.5 g).

Workup

  1. customThe Grignard solution is separated from the excess of magnesium
  2. temperaturemaintaining the temperature at -40° C
  3. stirringThe mixture is stirred vigorously for 1 hour
  4. temperatureto warm up to room temperature
  5. customThe organic phase is separated
  6. extractionextracted with 2 N HCl
  7. extractionBasification with concentrated ammonia (pH ~9-10), extraction with ether
  8. customdrying
  9. customevaporation

Sources & evidence

ORD record
ord-cf812cdd388f40c282d2623d4a68ff30
Source dataset
uspto-grants-1983_09
Patent number
US04405530

Linked notes

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