Ammonia → 2-Amino-4-(benzyloxy)-2-methylbutanonitrile
Reaction equation
[Cl-].[NH4+:2].[NH3:3].[C-:4]#N.[Na+].[CH2:7]([O:14][CH2:15][CH2:16][C:17](=O)[CH3:18])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>O.C(O)C.C(Cl)Cl>[NH2:2][C:17]([CH3:18])([CH2:16][CH2:15][O:14][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:4]#[N:3]Participants
Conditions
- Temperature
- 60 °C
Procedure
6.37 g (119.1 mmol) of ammonium chloride (dissolved in 15 ml of warm water) and 9 ml (216.6 mmol) of conc. ammonia in water were added to 5.31 g (108.3 mmol) of sodium cyanide in 10 ml of water. 19.3 g (108.3 mmol) of 4-(benzyloxy)butan-2-one, dissolved in 3 ml of ethanol, were then added. The mixture was stirred at RT for 15 min and at 60° C. for 2 h. Another 4 g (81.6 mmol) of sodium cyanide, 4.8 g (89.7 mmol) of ammonium chloride and 6.5 ml (156.4 mmol) of conc. ammonia in water were added and the mixture was stirred at 60° C. for a further 2 h. The reaction solution was then cooled, and 300 ml each of methylenechloride and water were added. After phase separation, the aqueous phase was extracted with 300 ml of methylene chloride. The combined organic phases were dried and concentrated. The crude product was purified on silica gel (cyclohexane/ethyl acetate gradient 6/4-1/1). This gave 19.9 g of the target compound (77% pure, 69% of theory).
Workup
- additionwere then added
- stirringthe mixture was stirred at 60° C. for a further 2 h
- temperatureThe reaction solution was then cooled
- customAfter phase separation
- extractionthe aqueous phase was extracted with 300 ml of methylene chloride
- customThe combined organic phases were dried
- concentrationconcentrated
- customThe crude product was purified on silica gel (cyclohexane/ethyl acetate gradient 6/4-1/1)
Sources & evidence
- ORD record
- ord-a89c3f736d854f34ab8c14717e35d666
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09126998B2
Reaction notes
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