Bromoacetonitrile → (S)-cyanomethyl 4-(methylthio)-4-oxo-2-(pent-4-enamido)butanoate

HRID 1482184Notes

Reaction equation

HRID 1482184 reaction equation
Br[CH2:2][C:3]#[N:4].C(N(C(C)C)C(C)C)C.[CH3:14][S:15][C:16](=[O:29])[CH2:17][C@H:18]([NH:22][C:23](=[O:28])[CH2:24][CH2:25][CH:26]=[CH2:27])[C:19]([OH:21])=[O:20].[Cl-].[NH4+]>CN(C=O)C>[CH3:14][S:15][C:16](=[O:29])[CH2:17][C@H:18]([NH:22][C:23](=[O:28])[CH2:24][CH2:25][CH:26]=[CH2:27])[C:19]([O:21][CH2:2][C:3]#[N:4])=[O:20]

Participants

6

Reactant 4

HCID 11534BromoacetonitrileHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 89668301(S)-4-(methylthio)-4-oxo-2-(pent-4-enamido)butanoic acid

Product 1

HCID 89668248(S)-cyanomethyl 4-(methylthio)-4-oxo-2-(pent-4-enamido)butanoateYield 34.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Bromoacetonitrile (2.64 ml, 37.8 mmol) and N-ethyl-N-isopropylpropan-2-amine (3.29 ml, 18.9 mmol) were added to a solution of (S)-4-(methylthio)-4-oxo-2-(pent-4-enamido)butanoic acid (Compound 1f-IA) (1.17 g, 3.78 mmol) in DMF (5 ml), and the mixture was stirred at room temperature for 30 minutes. A saturated aqueous ammonium chloride solution (3 ml) was added to the reaction mixture, after which the mixture was extracted with ethyl acetate and the organic layer was washed with water. The organic extract was then dried over magnesium sulfate. Following concentration under reduced pressure, the resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=100/0→30/70) to afford (S)-cyanomethyl 4-(methylthio)-4-oxo-2-(pent-4-enamido)butanoate (Compound 1g-IA) (368 mg, 34%).

Workup

  1. extractionafter which the mixture was extracted with ethyl acetate
  2. washthe organic layer was washed with water
  3. extractionThe organic extract
  4. dry with materialwas then dried over magnesium sulfate
  5. concentrationconcentration under reduced pressure
  6. customthe resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=100/0→30/70)

Sources & evidence

ORD record
ord-4247b3514fe74aeaa51f6c78e18ca0cc
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

Loading…