Water → Boc-Gly-Ala-Gly-DAla-Gly-OBzl

HRID 2287821Notes

Reaction equation

HRID 2287821 reaction equation
[NH:1]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:2][C:3]([NH:5][C@H:6]([C:8]([NH:10][CH2:11][C:12]([OH:14])=O)=[O:9])[CH3:7])=[O:4].C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.Cl.[NH2:45][C@@H:46]([C:48]([NH:50][CH2:51][C:52]([O:54][CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)=[O:53])=[O:49])[CH3:47].Cl>CN(C=O)C>[NH:1]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:2][C:3]([NH:5][C@H:6]([C:8]([NH:10][CH2:11][C:12]([NH:45][C@@H:46]([C:48]([NH:50][CH2:51][C:52]([O:54][CH2:55][C:56]1[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=1)=[O:53])=[O:49])[CH3:47])=[O:14])=[O:9])[CH3:7])=[O:4]

Participants

7

Reactant 5

HCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 131712174H-(D)Ala-Gly-OBzl.hydrochlorideHCID 131719922Boc-Gly-Ala-Gly

Product 1

HCID 131719921Boc-Gly-Ala-Gly-DAla-Gly-OBzlYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of Boc-Gly-Ala-Gly prepared as in Example 34B (11.0 g, 36.5 mmol) in anhydrous DMF (270 ml), was added HOBT.H2O (5.46 g, 40.4 mmol), EDC.HCl (7.74 g, 40.4 mmol), and DAla-Gly-OBzl.HCl prepared as in Example 34A (9.95 g, 36.5 mmol). The pH of the resulting solution was adjusted to ~8 (measured by spotting the reaction mixture on moistened Hydrion paper) and the reaction mixture was allowed to stir at room temperature for 12 h thereafter. The solution was concentrated in vacuo and the residue was dissolved in water (50 ml). This solution was extracted with ethyl acetate (3×100 ml). The combined ethyl acetate layers were washed with 1 N sodium bisulfate (50 ml), saturated sodium bicarbonate (50 ml) and brine (50 ml). The ethyl acetate solution was dried (magnesium sulfate), filtered and allowed to sit for 12 h undisturbed. Collection of the crystals by filtration and drying at high vacuum afforded 13.4 g (70% yield) of pure product: 1H NMR (DMSO-d6) δ 1.22 (d, J=7.2 Hz, 3 H), 1.23 (d, J=7.2 Hz, 3 H), 1.38 (s, 9 H), 3.58 (d, J=6.0 Hz, 2 H), 3.73 (d, J=4.8 Hz, 2 H), 3.91 (dd, J=6.0, 3.0 Hz, 2 H), 4.32 (m, 2 H), 5.14 (s, 2 H), 6.91 (t, J=4.8 Hz, 1 H), 7.38 (s, 5 H), 7.97 (d, J=8.1 Hz, 1 H), 8.02 (d, J=6.9 Hz, 1 H), 8.19 (t, J=5.4 Hz, 1 H), 8.33 (t, J=5.4 Hz, 1 H).

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. dissolutionthe residue was dissolved in water (50 ml)
  3. extractionThis solution was extracted with ethyl acetate (3×100 ml)
  4. washThe combined ethyl acetate layers were washed with 1 N sodium bisulfate (50 ml), saturated sodium bicarbonate (50 ml) and brine (50 ml)
  5. dry with materialThe ethyl acetate solution was dried (magnesium sulfate)
  6. filtrationfiltered
  7. waitto sit for 12 h
  8. customCollection of the crystals
  9. filtrationby filtration
  10. customdrying at high vacuum

Sources & evidence

ORD record
ord-59e02fc2553745cbb5e2211a83ea0dea
Source dataset
uspto-grants-2000_07
Patent number
US06084093

Reaction notes

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