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

HRID 1972654Notes

Reaction equation

HRID 1972654 reaction equation
[CH3:1][O:2][C:3]1[C:8]([CH2:9][C@@H:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[NH2:11])=[CH:7][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:8]1[C:3]([O:2][CH3:1])=[N:4][CH:5]=[CH:6][CH:7]=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 66582765Ethyl 3-(2-methoxy-3-pyridinyl)alaninate

Product 1

HCID 66582982ethyl N-(tert-butoxycarbonyl)glycyl-3-(2-methoxy-3-pyridinyl)alaninateYield 92.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a 100-mL round-bottomed flask was added ethyl 3-(2-methoxy-3-pyridinyl)alaninate (0.877 g, 3.91 mmol), N-α-t-Boc-glycine (0.753 g, 4.30 mmol, Aldrich, St. Louis, Mo.), HATU (1.784 g, 4.69 mmol, Aldrich, St. Louis, Mo.) and N,N-diisopropylethylamine (2.05 mL, 11.73 mmol, Aldrich, St. Louis, Mo.) in DMF (8 mL). The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with water (30 mL) and extracted with EtOAc (2×50 mL). The organic extract was washed with saturated NaCl (20 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-butoxy carbonyl)glycyl-3-(2-methoxy-3-pyridinyl)alaninate (1.38 g) as a colorless oil.

Workup

  1. extractionextracted with EtOAc (2×50 mL)
  2. extractionThe organic extract
  3. washwas washed with saturated NaCl (20 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-61927d2def034edd9f134c8eb951d376
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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