1-Fluoro-2-nitrobenzene → (2S,3S)-2-tert-butoxycarbonylamino-3-(2-nitro-phenylamino)-butyric acid methyl ester

HRID 1486030Notes

Reaction equation

HRID 1486030 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C@@H:4]([NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C@@H:5]([NH2:7])[CH3:6].F[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[N+:24]([O-:26])=[O:25].C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:1][O:2][C:3](=[O:16])[C@@H:4]([NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C@@H:5]([NH:7][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[N+:24]([O-:26])=[O:25])[CH3:6]

Participants

5

Reactant 3

HCID 738951-Fluoro-2-nitrobenzeneHCID 516892Sodium BicarbonateHCID 59984513methyl (2S,3S)-3-amino-2-{[(tert-butoxy)carbonyl]amino}butanoate

Product 1

HCID 90079370(2S,3S)-2-tert-butoxycarbonylamino-3-(2-nitro-phenylamino)-butyric acid methyl esterYield 78.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension (2S,3S)-3-amino-2-tert-butoxycarbonylamino-butyric acid methyl ester (6.0 g, 20.7 mmol) (prepared according to WO 2010031750), 1-fluoro-2-nitrobenzene (4.37 g, 31.0 mmol) and sodium hydrogen carbonate (5.21 g, 62 mmol) in N,N-dimethylformamide (60 ml) was heated to 85° C. for 24 h. The reaction was cooled, concentrated in vacuo and the residue was diluted with water (100 ml) and extracted with ethyl acetate (2×150 ml). The organic layers were combined, washed with water (1×50 mL), brine (1×50 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by chromatography over silica gel gradient eluted with 5 to 60% v/v ethyl acetate hexanes to give (2S,3S)-2-tert-butoxycarbonylamino-3-(2-nitro-phenylamino)-butyric acid methyl ester (5.71 g, 78%).

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated in vacuo
  3. additionthe residue was diluted with water (100 ml)
  4. extractionextracted with ethyl acetate (2×150 ml)
  5. washwashed with water (1×50 mL), brine (1×50 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by chromatography over silica gel gradient
  10. washeluted with 5 to 60% v/v ethyl acetate hexanes

Sources & evidence

ORD record
ord-d3ff659803ce4b8ea84ba7a969da814f
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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