Sodium Hydroxide → (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:15]([O:19][C:20]([NH:22][CH2:23][C:24](O)=[O:25])=[O:21])([CH3:18])([CH3:17])[CH3:16].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[OH-].[Na+]>C(Cl)Cl>[C:15]([O:19][C:20]([NH:22][CH2:23][C:24]([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:25])=[O:21])([CH3:18])([CH3:17])[CH3:16]Participants
7
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 25 °C
Procedure
A solution of (R)-3-amino-1-(4-chlorobenzyl)pyrrolidine (3.35 g, 16 mmol) in CH2Cl2 (80 mL) was treated with Et2N (2.5 mL, 17.6 mmol), N-tert-butoxycarbonylglycine (2.79 g, 16.0 mmol), EDCI (3.07 g, 16.0 mmol) and HOBt (2.16 g, 16 mmol). After the reaction mixture was stirred at 25° C. for 16 h, 2 N NaOH solution (80 mL) was added. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (100 mL×3). The combined organic layer was washed with water (100 mL×2) and brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. Column chromatography (SiO2, ethyl acetate) afforded the desired (R)-3-{N-(tert-butoxycarbonyl)glycyl}amino 1-(4-chlorobenzyl)pyrrolidine (5.40 g, 92%).
Workup
- customThe organic layer was separated
- extractionthe aqueous layer was extracted with dichloromethane (100 mL×3)
- washThe combined organic layer was washed with water (100 mL×2) and brine (100 mL)
- dry with materialdried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-eb04f6ff08bd477ea8626a22751d74ab
- Source dataset
- uspto-grants-2002_09
- Patent number
- US06451842B1
Reaction notes
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