Water → Boc-Gly-Ala-DAla-Gly-Gly-OBzl

HRID 363409Notes

Reaction equation

HRID 363409 reaction equation
[NH:1]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:2][C:3]([NH:5][C@H:6]([C:8]([OH:10])=O)[CH3:7])=[O:4].C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.Cl.[NH2:41][C@@H:42]([C:44]([NH:46][CH2:47][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])=[O:45])[CH3:43].Cl>CN(C=O)C>[NH:1]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:2][C:3]([NH:5][C@H:6]([C:8]([NH:41][C@@H:42]([C:44]([NH:46][CH2:47][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])=[O:45])[CH3:43])=[O:10])[CH3:7])=[O:4]

Participants

7

Reactant 5

HCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11128590Boc-Gly-Ala-OHHCID 131721129DAla-Gly-Gly-OBzl.HCl

Product 1

HCID 131719920Boc-Gly-Ala-DAla-Gly-Gly-OBzlYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of Boc-Gly-Ala prepared as in Example 33B (10.2 g, 41.5 mmol) in anhydrous DMF (300 ml), was added HOBT.H2O (6.21 g, 46.0 mmol), EDC.HCl (8.81 g, 46.0 mmol) and DAla-Gly-Gly-OBzl.HCl (13.7 g, 41.5 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 (40 ml). The resulting solution was extracted with ethyl acetate (3×150 ml). The combined ethyl acetate layers were washed with 1N sodium bisulfate (100 ml), saturated sodium bicarbonate (100 ml) and brine (100 ml). The ethyl acetate solution was dried (magnesium sulfate), filtered and concentrated to half volume. The product crystallized out upon standing at RT for 30 min. Collection of the crystals by filtration and drying at high vacuum afforded 17.4 g (80% yield) of the pure product: 1H NMR (DMSO-d6) δ 1.21 (d, J=7.4 Hz, 3 H), 1.23 (d, J=7.3 Hz, 3 H), 1.38 (s, 9 H), 3.56 (d, J=6.3 Hz, 2 H), 3.75 (d, J=5.7 Hz, 2 H), 3.93 (d, J=6.0 Hz, 2 H), 4.24-4.34 (m, 2 H), 5.14 (s, 2 H), 6.98 (t, J=5.7 Hz, 1 H), 7.34-7.40 (m, 5 H), 7.93 (d, J=7.2 Hz, 1 H), 8.17-8.24 (m, 3 H).

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. dissolutionthe residue was dissolved in water (40 ml)
  3. extractionThe resulting solution was extracted with ethyl acetate (3×150 ml)
  4. washThe combined ethyl acetate layers were washed with 1N sodium bisulfate (100 ml), saturated sodium bicarbonate (100 ml) and brine (100 ml)
  5. dry with materialThe ethyl acetate solution was dried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated to half volume
  8. customThe product crystallized out
  9. waitupon standing at RT for 30 min
  10. customCollection of the crystals
  11. filtrationby filtration
  12. customdrying at high vacuum

Sources & evidence

ORD record
ord-c07e131b1cc04df6820e6e936ab6e754
Source dataset
uspto-grants-1999_02
Patent number
US05874421

Reaction notes

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