Carbon Dioxide → N-CBZ-D-phenylalanyl-L-valyl-L-alanine

HRID 345221Notes

Reaction equation

HRID 345221 reaction equation
[CH2:1](N(CC)CC)C.[NH:8]1C[CH2:19][CH2:18][C@H:9]1[C:10]([NH:12][C@H:13]([C:15]([OH:17])=[O:16])[CH3:14])=[O:11].C(=O)=O.[N+](C1C=CC(O[C:34](=[O:54])[C@@H:35]([CH2:47][C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[NH:36][C:37]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[O:38])=CC=1)([O-])=O.Cl>O1CCOCC1.O.C(OCC)(=O)C>[C:37]([NH:36][C@@H:35]([C:34]([NH:8][C@H:9]([C:10]([NH:12][C@H:13]([C:15]([OH:17])=[O:16])[CH3:14])=[O:11])[CH:18]([CH3:19])[CH3:1])=[O:54])[CH2:47][C:48]1[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=1)([O:39][CH2:40][C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)=[O:38]

Participants

8

Reactant 5

HCID 280Carbon DioxideHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 6347578L-Prolyl-L-alanineHCID 12448569N-((Phenylmethoxy)carbonyl)-D-phenylalanine 4-nitrophenyl ester

Product 1

HCID 18647210N-CBZ-D-phenylalanyl-L-valyl-L-alanineYield 69%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

Triethylamine (9.0 mmol, 1.25 mL) was added to a mixture of L-prolyl-L-alanine (Sigma, 4.5 mmol, 838 mg) in 80 mL of 1:1 dioxane-water. After 15 minutes, pieces of solid carbon dioxide were added to the solution until the pH was reduced to pH 8. N-CBZ-D-Phenylalanine 4-nitrophenyl ester (Sigma, 4.5 mmol, 1.89 g) was then added, and the mixture was stirred at room temperature for four days. The clear yellow solution was acidified by gradual addition of 1 N HCl, and diluted with ethyl acetate. The organic phase was then separated, washed with water (3×) and brine (2×), dried (MgSO4), and rotary evaporated to give an oil residue. A solution of this residue in ethyl acetate was fractionally extracted with three solutions of 80 mg NaHCO3 in 10 mL water. These aqueous extracts were combined, acidified, and extracted with ethyl acetate. The resulting ethyl acetate solution was washed with brine, dried (MgSO4), evaporated, and dried at high vacuum to provide 1.45 g (69%) of N-CBZ-D-phenylalanyl-L-valyl-L-alanine as a viscous oil, in sufficient purity for the next step.

Workup

  1. customThe organic phase was then separated
  2. washwashed with water (3×) and brine (2×)
  3. dry with materialdried (MgSO4)
  4. customrotary evaporated
  5. customto give an oil residue
  6. extractionA solution of this residue in ethyl acetate was fractionally extracted with three solutions of 80 mg NaHCO3 in 10 mL water
  7. extractionextracted with ethyl acetate
  8. washThe resulting ethyl acetate solution was washed with brine
  9. dry with materialdried (MgSO4)
  10. customevaporated
  11. customdried at high vacuum

Sources & evidence

ORD record
ord-e2399fc19bcb4ba2adc60f24b2a41109
Source dataset
uspto-grants-1991_10
Patent number
US05055451

Reaction notes

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