N-(tert-butoxycarbonyl)glycine → ethyl N-(tert-butoxycarbonyl)glycyl-3-(2-methoxy-4-pyridinyl)alaninate

HRID 1972670Notes

Reaction equation

HRID 1972670 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH2:9][C@@H:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[NH2:11])[CH:6]=[CH:5][N:4]=1.[CH3:17][C:18]([O:21][C:22]([NH:24][CH2:25][C:26](O)=[O:27])=[O:23])([CH3:20])[CH3:19].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C.O>[C:18]([O:21][C:22]([NH:24][CH2:25][C:26]([NH:11][C@H:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:9][C:7]1[CH:6]=[CH:5][N:4]=[C:3]([O:2][CH3:1])[CH:8]=1)=[O:27])=[O:23])([CH3:20])([CH3:19])[CH3:17]

Participants

7

Reactant 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66582735Ethyl 3-(2-methoxy-4-pyridinyl)alaninate

Product 1

HCID 66582764ethyl N-(tert-butoxycarbonyl)glycyl-3-(2-methoxy-4-pyridinyl)alaninateYield 92.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a 100-mL round-bottomed flask was added ethyl 3-(2-methoxy-4-pyridinyl)alaninate (1.47 g, 6.56 mmol), N-α-t-boc-glycine (1.26 g, 7.22 mmol, Aldrich, St. Louis, Mo.), HATU (2.99 g, 7.87 mmol, Aldrich, St. Louis, Mo.) and N,N-diisopropylethylamine (3.42 mL, 19.68 mmol, Aldrich, St. Louis, Mo.) in DMF (6 mL). The reaction mixture was stirred room temperature for 18 h, diluted with water (50 mL), and extracted with EtOAc (2×20 mL). The organic extract was washed with saturated NaCl (30 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a light-yellow oil. The crude product was purified by silica gel chromatography, eluting with 60% EtOAc/hexanes to give ethyl N-(tert-butoxycarbonyl)glycyl-3-(2-methoxy-4-pyridinyl)alaninate (2.31 g) as a colorless oil.

Workup

  1. extractionextracted with EtOAc (2×20 mL)
  2. extractionThe organic extract
  3. washwas washed with saturated 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 a light-yellow oil
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with 60% EtOAc/hexanes

Sources & evidence

ORD record
ord-32396c541b914fb5b8e350c985bca66a
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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