Triethylamine → (R)-3-[[N-(2-(tert-butoxycarbonylamino)-5-trifluoromethylbenzoyl)glycyl]amino]-1-(4-chlorobenzyl)pyrrolidine

HRID 133559Notes

Reaction equation

HRID 133559 reaction equation
C(N(CC)CC)C.[C:8]([O:12][C:13]([NH:15][C:16]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][C:17]=1[C:18]([OH:20])=O)=[O:14])([CH3:11])([CH3:10])[CH3:9].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl:50][C:51]1[CH:67]=[CH:66][C:54]([CH2:55][N:56]2[CH2:60][CH2:59][C@@H:58]([NH:61][C:62](=[O:65])[CH2:63][NH2:64])[CH2:57]2)=[CH:53][CH:52]=1.[OH-].[Na+]>ClCCl>[C:8]([O:12][C:13]([NH:15][C:16]1[CH:24]=[CH:23][C:22]([C:25]([F:26])([F:27])[F:28])=[CH:21][C:17]=1[C:18]([NH:64][CH2:63][C:62]([NH:61][C@@H:58]1[CH2:59][CH2:60][N:56]([CH2:55][C:54]2[CH:53]=[CH:52][C:51]([Cl:50])=[CH:67][CH:66]=2)[CH2:57]1)=[O:65])=[O:20])=[O:14])([CH3:9])([CH3:10])[CH3:11]

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 150338862-((tert-Butoxycarbonyl)amino)-5-(trifluoromethyl)benzoic acidHCID 54551710(R)-1-(4-chlorobenzyl)-3-(glycylamino)pyrrolidine

Product 1

HCID 54203221(R)-3-[[N-(2-(tert-butoxycarbonylamino)-5-trifluoromethylbenzoyl)glycyl]amino]-1-(4-chlorobenzyl)pyrrolidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethylamine (2.9 mL, 20.5 mmol), 2-(tert-butoxycarbonylamino)-5-(trifluoromethyl)benzoic acid (6.27 g, 20.5 mmol), EDCI (3.9 g, 20.5 mmol) and HOBt (2.8 g, 20.5 mmol) were added to a dichloromethane (100 mL) solution of (R)-1-(4-chlorobenzyl)-3-(glycylamino)pyrrolidine (5.0 g, 18.7 mmol). The resulting reaction mixture was stirred at room temperature overnight. A 2 M aqueous solution (80 mL) of NaOH was added to the reaction mixture, and the resulting mixture was extracted with dichloromethane. The obtained extract was dried over anhydrous Na2SO4, filtered, concentrated and purified by column chromatography [SiO2, hexane/ethyl acetate=(1:1) to (1:4)] to thereby afford (R)-3-[[N-(2-(tert-butoxycarbonylamino)-5-trifluoromethylbenzoyl)glycyl]amino]-1-(4-chlorobenzyl)pyrrolidine (9.41 g, 91%) as a white amorphous solid. ESI/MS m/e 555.2 (M++H, C26H30ClF3N4O4).

Workup

  1. customThe resulting reaction mixture
  2. extractionthe resulting mixture was extracted with dichloromethane
  3. extractionThe obtained extract
  4. dry with materialwas dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by column chromatography [SiO2, hexane/ethyl acetate=(1:1) to (1:4)] to thereby afford (R)-3-[[N-(2-(tert-butoxycarbonylamino)-5-trifluoromethylbenzoyl)glycyl]amino]-1-(4-chlorobenzyl)pyrrolidine (9.41 g, 91%) as a white amorphous solid

Sources & evidence

ORD record
ord-59edacd4ebbc45d7ac8a9bce11c098b3
Source dataset
uspto-grants-2008_06
Patent number
US07390830B1

Reaction notes

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