Bromoacetonitrile → (R)-cyanomethyl 2-((((4,5-dimethoxy-2-nitrobenzyl)oxy)carbonyl)(methyl)amino)-3-(ethyldisulfanyl)propanoate

HRID 1482211Notes

Reaction equation

HRID 1482211 reaction equation
Br[CH2:2][C:3]#[N:4].C(N(C(C)C)C(C)C)C.[CH3:14][O:15][C:16]1[C:36]([O:37][CH3:38])=[CH:35][C:19]([CH2:20][O:21][C:22]([N:24]([CH3:34])[C@@H:25]([CH2:29][S:30][S:31][CH2:32][CH3:33])[C:26]([OH:28])=[O:27])=[O:23])=[C:18]([N+:39]([O-:41])=[O:40])[CH:17]=1.[Cl-].[NH4+]>CN(C=O)C>[CH3:14][O:15][C:16]1[C:36]([O:37][CH3:38])=[CH:35][C:19]([CH2:20][O:21][C:22]([N:24]([CH3:34])[C@@H:25]([CH2:29][S:30][S:31][CH2:32][CH3:33])[C:26]([O:28][CH2:2][C:3]#[N:4])=[O:27])=[O:23])=[C:18]([N+:39]([O-:41])=[O:40])[CH:17]=1

Participants

6

Reactant 4

HCID 11534BromoacetonitrileHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 89668435(R)-2-((((4,5-dimethoxy-2-nitrobenzyl)oxy) carbonyl)(methyl)amino)-3-(ethyldisulfanyl)propanoic acid2×

Product 1

HCID 89668261(R)-cyanomethyl 2-((((4,5-dimethoxy-2-nitrobenzyl)oxy)carbonyl)(methyl)amino)-3-(ethyldisulfanyl)propanoateYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Bromoacetonitrile (0.115 ml, 1.65 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.105 ml, 0.604 mmol) were added to a solution of (R)-2-((((4,5-dimethoxy-2-nitrobenzyl)oxy)carbonyl)(methyl)amino)-3-(ethyldisulfanyl)propanoic acid (Compound 2k-F) (238 mg, 0.549 mmol) in DMF (2.5 ml), and the mixture was stirred at room temperature for 10 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 reverse-phase silica gel column chromatography (10 mM aqueous ammonium acetate solution/methanol=70/30→0/100) to afford (R)-cyanomethyl 2-((((4,5-dimethoxy-2-nitrobenzyl)oxy) carbonyl)(methyl)amino)-3-(ethyldisulfanyl)propanoate (Compound 21-F) (221 mg, 85%).

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 reverse-phase silica gel column chromatography (10 mM aqueous ammonium acetate solution/methanol=70/30→0/100)

Sources & evidence

ORD record
ord-bc66c009613042899f19b3c2decf7143
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

Loading…