L-Proline → N-Carbobenzoxy-beta-Benzyl-L-Aspartyl-L-Proline

HRID 249068Notes

Reaction equation

HRID 249068 reaction equation
[NH:1]1[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=[O:4].[N+](C1C=CC([O:18][C:19](=O)[C@H:20]([CH:32]([CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:33]([OH:35])=[O:34])[NH:21][C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])=CC=1)([O-])=O>CN(C)C=O>[C:22]([NH:21][C@H:20]([C:19]([N:1]1[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=[O:4])=[O:18])[CH:32]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:33](=[O:34])[OH:35])([O:24][CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)=[O:23]

Participants

4

Reactant 2

HCID 145742L-ProlineHCID 53721982HCID 53721982, compound

Product 1

HCID 54163294N-Carbobenzoxy-beta-Benzyl-L-Aspartyl-L-Proline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

L-Proline (2.8 Kg) and N-carbobenzoxy-β-benzyl-L-aspartic acid p-nitrophenyl ester (10.5 Kg) are dissolved in a mixture of dimethylformamide (25-30 L) and distilled water (9-13 L). The pH of the solution is adjusted to 7.5-8.0 and maintained in this range by addition of diisopropylethylamine. The mixture is stirred at 20°-30° C. until the reaction is complete. The solution is diluted with ethyl acetate (45-55 L) and extracted with dilute hydrochloric acid (15-20 L). The aqueous layer is back extracted with ethyl acetate (8-12 L). The combined organic layers are washed three times with dilute hydrochloric acid (10-15 L). The organic layer is extracted with dilute sodium bicarbonate. Ethyl acetate (40-60 L) is added to the aqueous layer and the pH is adjusted to about 3.0 by addition of dilute hydrochloric acid. The organic layer is washed two times with dilute hydrochloric acid (10-30 L) and concentrated in vacuo below 55° C. to 20-30 L.

Workup

  1. distillationdistilled water (9-13 L)
  2. temperaturemaintained in this range by addition of diisopropylethylamine
  3. additionThe solution is diluted with ethyl acetate (45-55 L)
  4. extractionextracted with dilute hydrochloric acid (15-20 L)
  5. extractionThe aqueous layer is back extracted with ethyl acetate (8-12 L)
  6. washThe combined organic layers are washed three times with dilute hydrochloric acid (10-15 L)
  7. extractionThe organic layer is extracted with dilute sodium bicarbonate
  8. additionEthyl acetate (40-60 L) is added to the aqueous layer
  9. additionthe pH is adjusted to about 3.0 by addition of dilute hydrochloric acid
  10. washThe organic layer is washed two times with dilute hydrochloric acid (10-30 L)
  11. concentrationconcentrated in vacuo below 55° C. to 20-30 L

Sources & evidence

ORD record
ord-323361ec6be941388e100680e54f3ab0
Source dataset
uspto-grants-1993_05
Patent number
US05212287

Reaction notes

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