Carbon Dioxide → Z-Pro-val-OH

HRID 345220Notes

Reaction equation

HRID 345220 reaction equation
[NH2:1][C@H:2]([C:6]([OH:8])=[O:7])[CH:3]([CH3:5])[CH3:4].C(N(CC)CC)C.C(=O)=O.[N+](C1C=CC([O:28][C:29](=O)[C@@H:30]2[CH2:34][CH2:33][CH2:32][N:31]2[C:35]([O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[O:36])=CC=1)([O-])=O.Cl>O1CCOCC1.O>[C:35]([N:31]1[CH2:32][CH2:33][CH2:34][C@H:30]1[C:29]([NH:1][C@H:2]([C:6]([OH:8])=[O:7])[CH:3]([CH3:5])[CH3:4])=[O:28])([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:36]

Participants

7

Reactant 5

HCID 280Carbon DioxideHCID 313Hydrochloric AcidHCID 6287L-ValineHCID 8471TriethylamineHCID 10133728Z-Pro-ONp

Product 1

HCID 73512Z-Pro-val-OHYield 68.4%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

L-Valine (30 mmol, 3.52 g) and triethylamine (60 mmol, 8.36 mL) were combined in 275 mL of 1:1 dioxane-water. Solid carbon dioxide pieces were added with stirring to achieve pH 8.5, and then N-CBZ-L-proline 4-nitrophenyl ester (Sigma, 30 mmol, 11.11 g) was added to the solution with stirring at room temperature. After 20 hours, the clear yellow solution was acidified by gradual addition of 1 N HCl, concentrated by rotary evaporation at reduced pressure, and diluted with ethyl acetate. The organic phase was separated, washed with water (5×) and brine (2×), dried (MgSO4), and rotovapped to give an oil residue. Crystallization of this residue from hot ethyl acetate-hexane afforded 7.15 g (68%) of N-CBZ-L-prolyl-L-valine as a white solid, m.p. 132°-134° C., lit. m.p. 134°-136° C.; G. R. Pettit, "Synthetic Peptides," Vol. 1, 154 (1970).

Workup

  1. stirringwith stirring at room temperature
  2. concentrationconcentrated by rotary evaporation at reduced pressure
  3. additiondiluted with ethyl acetate
  4. customThe organic phase was separated
  5. washwashed with water (5×) and brine (2×)
  6. dry with materialdried (MgSO4)
  7. customto give an oil residue
  8. customCrystallization of this residue from hot ethyl acetate-hexane

Sources & evidence

ORD record
ord-50b665185c02401c9061ef3930c2728f
Source dataset
uspto-grants-1991_10
Patent number
US05055451

Reaction notes

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