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1-Hydroxybenzotriazole → (S)-2-[[(S)-2-(Acetoxyacetyl)-1-pyrrolidinyl]carbonyl]-N-(phenylmethyl)-1-pyrrolidinecarboxamide

HRID 1735391
Notes
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Reaction equation

HRID 1735391 reaction equation
[C:1]([O:4][CH2:5][C:6]([C@@H:8]1[CH2:12][CH2:11][CH2:10][N:9]1[C:13]([O:15]C(C)(C)C)=O)=[O:7])(=[O:3])[CH3:2].[NH:20]1[CH2:27][CH2:26][CH2:25][C@H:21]1C(O)=O.[CH2:28]([N:35]=[C:36]=[O:37])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C1C=CC2N(O)N=NC=2C=1>FC(F)(F)C(O)=O.C(O)(=O)C.CN(C=O)C.C(Cl)Cl.O.C(N(CC)CC)C>[C:1]([O:4][CH2:5][C:6]([C@@H:8]1[CH2:12][CH2:11][CH2:10][N:9]1[C:13]([C@@H:27]1[CH2:26][CH2:25][CH2:21][N:20]1[C:36]([NH:35][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:37])=[O:15])=[O:7])(=[O:3])[CH3:2]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

10

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 76639Benzyl isocyanateHCID 145742L-ProlineHCID 13753435(S)-2-(Acetoxyacetyl)-1-(tert-butoxycarbonyl)pyrrolidine

Product 1

HCID 15389023(S)-2-[[(S)-2-(Acetoxyacetyl)-1-pyrrolidinyl]carbonyl]-N-(phenylmethyl)-1-pyrrolidinecarboxamideYield 40.8%

Reagents, catalysts & solvents

5
HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolventHCID 23437676Trifluoroacetic acid acetateSolvent

Procedure

(S)-2-(Acetoxyacetyl)-1-(tert-butoxycarbonyl)pyrrolidine (8.9 g) was dissolved in trifluoroacetic acid-acetic acid (1:1 solution, 90 ml), and the mixture was stirred at room temperature for 1.5 hours. The reaction mixture was concentrated under reduced pressure and the residue was suspended in methylene chloride. The suspension was added to a solution of N-(benzylaminocarbonyl)-L-proline obtained by stirring L-proline (4.0 g), benzyl isocyanate (3.9 g) and triethylamine (3.5 g) in DMF (40 ml) at room temperature for 1 hour. Then, HOBt (4.7 g) and water-soluble carbodiimide hydrochloride (6.7 g) were added. The mixture was stirred at room temperature overnight and methylene chloride was added to the reaction mixture. The resulting mixture was washed with 10% potassium hydrogensulfate, a saturated aqueous solution of sodium bicarbonate and water in order, dried over anhydrous sodium sulfate, and concentrated. The residue was dissolved in ethyl acetate, added with active charcoal, stirred at room temperature for 30 minutes, filtered and concentrated to give the title compound (4.8 g) (see Table 1).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionThe suspension was added to a solution of N-(benzylaminocarbonyl)-L-proline
  3. customobtained
  4. stirringThe mixture was stirred at room temperature overnight
  5. washThe resulting mixture was washed with 10% potassium hydrogensulfate
  6. dry with materiala saturated aqueous solution of sodium bicarbonate and water in order, dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in ethyl acetate
  9. additionadded with active charcoal
  10. stirringstirred at room temperature for 30 minutes
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-a356c5e06f984e8cb39c8958c1b4eb45
Source dataset
uspto-grants-1996_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05536737

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes