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

HRID 279258Notes

Reaction equation

HRID 279258 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][N:7]2[CH2:11][CH2:10][C@@H:9]([NH:12][C:13](=[O:16])[CH2:14][NH2:15])[CH2:8]2)=[CH:4][CH:3]=1.CCN(CC)CC.[C:26]([O:30][C:31]([NH:33][C:34]1[CH:42]=[CH:41][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:39][C:35]=1[C:36](O)=[O:37])=[O:32])([CH3:29])([CH3:28])[CH3:27].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[OH-].[Na+]>ClCCl>[C:26]([O:30][C:31]([NH:33][C:34]1[CH:42]=[CH:41][C:40]([C:43]([F:44])([F:45])[F:46])=[CH:39][C:35]=1[C:36]([NH:15][CH2:14][C:13]([NH:12][C@@H:9]1[CH2:10][CH2:11][N:7]([CH2:6][C:5]2[CH:17]=[CH:18][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH2:8]1)=[O:16])=[O:37])=[O:32])([CH3:29])([CH3:27])[CH3:28]

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)pyrrolidineYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-1-(4-chlorobenzyl)-3-(glycylamino)pyrrolidine (5.0 g, 18.7 mmol) in dichloromethane (100 mL) was treated with Et3N (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). The reaction mixture was stirred at room temperature overnight. To the reaction mixture was added 2 N aqueous NaOH solution (80 mL) and the mixture was extracted with dichloromethane. The extract was dried over anhydrous Na2SO4, filtered, and evaporated. Column chromatography (SiO2, hexane/ethyl acetate=1/1-1/4) afforded (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. extractionthe mixture was extracted with dichloromethane
  2. dry with materialThe extract was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. customevaporated

Sources & evidence

ORD record
ord-50488f2558794ca7a615c383c81e3a8d
Source dataset
uspto-grants-2002_03
Patent number
US06362177B1

Reaction notes

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