N-(tert-butoxycarbonyl)glycine → ethyl N-(tert-butoxycarbonyl)glycyl-3-methoxyphenylalaninate

HRID 1972546Notes

Reaction equation

HRID 1972546 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:14]=[CH:15][CH:16]=1)[CH2:6][C@@H:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[NH2:8].[C:17]([O:21][C:22]([NH:24][CH2:25][C:26](O)=[O:27])=[O:23])([CH3:20])([CH3:19])[CH3:18].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>O.CN(C=O)C>[C:17]([O:21][C:22]([NH:24][CH2:25][C:26]([NH:8][C@H:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:6][C:5]1[CH:14]=[CH:15][CH:16]=[C:3]([O:2][CH3:1])[CH:4]=1)=[O:27])=[O:23])([CH3:20])([CH3:19])[CH3:18]

Participants

7

Reactant 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 8027297ethyl (2S)-2-amino-3-(3-methoxyphenyl)propanoateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 66582631ethyl N-(tert-butoxycarbonyl)glycyl-3-methoxyphenylalaninateYield 91.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a 100-mL round-bottomed flask was added ethyl 3-methoxyphenylalaninate (526 mg, 2.35 mmol), 2-(tert-butoxycarbonylamino)acetic acid (454 mg, 2.59 mmol, Sigma-Aldrich, St. Louis, Mo.), HATU (1.07 g, 2.82 mmol, Sigma-Aldrich, St. Louis, Mo.), Hünig's base (0.819 mL, 4.71 mmol) and DMF (5 mL). The reaction mixture was stirred at room temperature for 2 h then diluted with water (30 mL) and extracted with EtOAc (2×50 mL). The organic extract was washed with saturated aqueous NaCl (30 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as light-yellow oil. The crude product was purified by silica gel chromatography, eluting with 60% EtOAc in hexanes to give ethyl N-(tert-butoxycarbonyl)glycyl-3-methoxyphenylalaninate (822 mg).

Workup

  1. extractionextracted with EtOAc (2×50 mL)
  2. extractionThe organic extract
  3. washwas washed with saturated aqueous NaCl (30 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationThe solution was filtered
  6. concentrationconcentrated in vacuo
  7. customto give the crude material as light-yellow oil
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with 60% EtOAc in hexanes

Sources & evidence

ORD record
ord-2dcd9ca70385444abfcc1629340b43f6
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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