Methanol → (R)-1-(4-butylbenzyl)-3-[[N-(3-trifluoromethylbenzoyl)glycyl]amino]pyrrolidine
Reaction equation
[F:1][C:2]([F:22])([F:21])[C:3]1[CH:4]=[C:5]([CH:18]=[CH:19][CH:20]=1)[C:6]([NH:8][CH2:9][C:10]([NH:12][C@@H:13]1[CH2:17][CH2:16][NH:15][CH2:14]1)=[O:11])=[O:7].[CH2:23]([C:27]1[CH:34]=[CH:33][C:30]([CH:31]=O)=[CH:29][CH:28]=1)[CH2:24][CH2:25][CH3:26].[BH3-]C#N.[Na+].CO>C(O)(=O)C>[CH2:23]([C:27]1[CH:28]=[CH:29][C:30]([CH2:31][N:15]2[CH2:16][CH2:17][C@@H:13]([NH:12][C:10](=[O:11])[CH2:9][NH:8][C:6](=[O:7])[C:5]3[CH:18]=[CH:19][CH:20]=[C:3]([C:2]([F:1])([F:21])[F:22])[CH:4]=3)[CH2:14]2)=[CH:33][CH:34]=1)[CH2:24][CH2:25][CH3:26]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 60 °C
Procedure
To a mixture of (R)-3-[N-(3-(trifluoromethyl)benzoyl)glycyl]aminopyrrolidine (0.050 mmol), 4-butylbenzaldehyde (0.18 mmol), NaBH3CN (0.23 mmol), and methanol (1.85 mL) was added acetic acid (0.060 mL). The reaction mixture was stirred at 60° C. for 12 h. The mixture was cooled to room temperature, loaded onto Varian™ SCX column, and washed with CH3OH (15 mL) . Product was eluted off using 2 N NH3 in CH3OH (5 mL) and concentrated to afford (R)-1-(4-butylbenzyl)-3-[{N-(3-trifluoromethylbenzoyl)glycyl}amino]pyrrolidine (Compound No. 1648) (20.6 mg, 89%): The purity was determined by RPLC/MS (9%); ESI/MS m/e 462.2 (M++H, C25H30F3N3O2)
Workup
- temperatureThe mixture was cooled to room temperature
- washwashed with CH3OH (15 mL)
- washProduct was eluted off
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-73bf12be42c647c1a8056ecc61868976
- Source dataset
- uspto-grants-2002_09
- Patent number
- US06451842B1
Reaction notes
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