Benzyl chloroformate → Benzyl 2-cyano-4-fluorobutan-2-ylcarbamate

HRID 1486273Notes

Reaction equation

HRID 1486273 reaction equation
Cl.[NH2:2][C:3]([CH3:9])([CH2:6][CH2:7][F:8])[C:4]#[N:5].C(=O)([O-])[O-].[K+].[K+].Cl[C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18]>O1CCCC1.O>[C:4]([C:3]([NH:2][C:17](=[O:18])[O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([CH2:6][CH2:7][F:8])[CH3:9])#[N:5]

Participants

5

Reactant 3

HCID 10387Benzyl chloroformate2×HCID 11430Potassium CarbonateHCID 117858402rac-2-Amino-4-fluoro-2-methylbutanonitrile hydrochloride

Product 1

HCID 90251292Benzyl 2-cyano-4-fluorobutan-2-ylcarbamate

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

The crude rac-2-amino-4-fluoro-2-methylbutanonitrile hydrochloride product from Example 72A was initially charged in 165 ml of tetrahydrofuran/water (1:1), and 28.57 g (206.71 mmol) of potassium carbonate and 9.46 g (55.46 mmol) of benzyl chloroformate were added. The reaction mixture (biphasic mixture) was stirred at room temperature overnight. Another 1.72 g (10.1 mmol) of benzyl chloroformate were added to the reaction and the mixture was stirred at room temperature for a further 2 h. Subsequently, the biphasic system was separated and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were washed once with saturated aqueous sodium chloride solution, and then dried over sodium sulphate, filtered and concentrated by rotary evaporation. The residue was purified by means of silica gel chromatography (eluent:cyclohexane/ethyl acetate gradient=20/1 to 5/1). 5.04 g of the target compound were obtained (38% of theory over two stages, 96% purity).

Workup

  1. stirringthe mixture was stirred at room temperature for a further 2 h
  2. customSubsequently, the biphasic system was separated
  3. extractionthe aqueous phase was extracted twice with ethyl acetate
  4. washThe combined organic phases were washed once with saturated aqueous sodium chloride solution
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporation
  8. customThe residue was purified by means of silica gel chromatography (eluent:cyclohexane/ethyl acetate gradient=20/1 to 5/1)

Sources & evidence

ORD record
ord-c9f06cb7d27b4afcbf69f3bd4df2e97d
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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