Dicyclohexylcarbodiimide → HCID 131717224, compound

HRID 2372877Notes

Reaction equation

HRID 2372877 reaction equation
[NH:1]([C:22]([O:24]C(C)(C)C)=O)[C@H:2]([C:7]([NH:9][CH2:10][C:11]([NH:13][O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:12])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5].Cl.CCOC(C)=O.C1C=CC2N(O)N=NC=2C=1.[N:46]1([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:54][C@H:52]([OH:53])[CH2:51][C@H:47]1C(O)=O.C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1>[N:46]1([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:54][C@H:52]([OH:53])[CH2:51][C@H:47]1[C:22]([NH:1][C@H:2]([C:7]([NH:9][CH2:10][C:11]([NH:13][O:14][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[O:12])=[O:8])[CH2:3][CH:4]([CH3:5])[CH3:6])=[O:24]

Participants

7

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acidHCID 14694706HCID 14694706, compoundHCID 21866389Hydrogen chloride-ethyl acetate

Product 1

HCID 131717224HCID 131717224, compoundYield 56.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To Boc-Leu-Gly-NHOBzl (3.89 g; 9.89 mmol) obtained in Example 1 (C) was added under ice cooling 4.5N-HCl/AcOEt (30 ml), and the solution was brought back to room temperature. The reaction was carried out for 1 hour. The solvent was distilled off under reduced pressure and the residue was dissolved in THF (100 ml). The solution was cooled with a coolant at -20° C. After TEA (1.40 ml; 10.0 mmol) was added dropwise, HOBt (1.22 g; 9.03 mmol) and Boc-Hyp-OH (1.99 g; 8.60 mmol) were added and DCC (2.31 g; 11.2 mmol) dissolved in THF (10 ml) was added dropwise. The reaction was carried out for 1 hour at -10° C. and overnight in a refrigerator. Insolubles were filtered off and the solvent was then distilled off under reduced pressure. The residue was dissolved in AcOEt and the solution was washed successively with water, 1N-HCl, water, 10% Na2CO3 and water and then dried over anhydrous MgSO4. The solvent was distilled off under reduced pressure and the residue was recrystallized from AcOEt to give Boc-Hyp-Leu-Gly-NHOBzl (2.45 g; 56%) as colorless crystals. m.p. 168°-173° C., specific rotation [α]D28 -50.8 (c= 1.0, EtOH).

Workup

  1. customwas brought back to room temperature
  2. distillationThe solvent was distilled off under reduced pressure
  3. dissolutionthe residue was dissolved in THF (100 ml)
  4. additionwas added dropwise
  5. waitThe reaction was carried out for 1 hour at -10° C. and overnight in a refrigerator
  6. filtrationInsolubles were filtered off
  7. distillationthe solvent was then distilled off under reduced pressure
  8. dissolutionThe residue was dissolved in AcOEt
  9. washthe solution was washed successively with water, 1N-HCl, water, 10% Na2CO3 and water
  10. dry with materialdried over anhydrous MgSO4
  11. distillationThe solvent was distilled off under reduced pressure
  12. customthe residue was recrystallized from AcOEt

Sources & evidence

ORD record
ord-20d8b09af3fa4edb849b5574418044c7
Source dataset
uspto-grants-1992_03
Patent number
US05100874

Reaction notes

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