Triethylamine → (R)-3-(N-(tert-butoxycarbonyl)glycyl)amino-1-(4-chlorobenzyl)pyrrolidine
Reaction equation
[NH2:1][C@@H:2]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)[CH2:3]1.C(N(CC)CC)C.[C:22]([O:26][C:27]([NH:29][CH2:30][C:31](O)=[O:32])=[O:28])([CH3:25])([CH3:24])[CH3:23].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[OH-].[Na+]>ClCCl>[C:22]([O:26][C:27]([NH:29][CH2:30][C:31]([NH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)[CH2:3]1)=[O:32])=[O:28])([CH3:25])([CH3:24])[CH3:23]Participants
Reactant 6
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 25 °C
Procedure
To a dichloromethane (80 mL) solution of the (R)-3-amino-1-(4-chlorobenzyl)pyrrolidine (3.35 g, 16 mmol), were added triethylamine (2.5 mL, 17.6 mmol), N-tert-butoxycarbonylglycine (2.79 g, 16.0 mmol), EDCI (3.07 g, 16.0 mmol) and HOBt (12.16 g, 16 mmol). The resulting reaction mixture was stirred at 25° C. for 16 hours, and a 2 M solution (80 mL) of NaOH was then added thereto. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (100 mL×3). The organic layers were combined, washed with water (100 mL×2) and brine (100 mL), dried over anhydrous sodium sulfate, filtered, concentrated and purified by column chromatography (SiO2, ethyl acetate) to thereby provide the objective (R)-3-[N-(tert-butoxycarbonyl)glycyl]amino-1-(4-chlorobenzyl)pyrrolidine (5.40 g, 92%).
Workup
- customThe resulting reaction mixture
- customThe organic layer was separated
- extractionthe aqueous layer was extracted with dichloromethane (100 mL×3)
- washwashed with water (100 mL×2) and brine (100 mL)
- dry with materialdried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- custompurified by column chromatography (SiO2, ethyl acetate)
Sources & evidence
- ORD record
- ord-102766b4e31e467aab5aee47b5408347
- Source dataset
- uspto-grants-2008_06
- Patent number
- US07390830B1
Reaction notes
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