Diisopropylethylamine → (2S,4R)-tert-butyl 4-cyano-2-(4-(4-fluorophenoxy)phenylcarbamoyl)pyrrolidine-1-carboxylate
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([C:13]#[N:14])[CH2:10][C@H:9]1[C:15]([OH:17])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:42][C:43]1[CH:56]=[CH:55][C:46]([O:47][C:48]2[CH:54]=[CH:53][C:51]([NH2:52])=[CH:50][CH:49]=2)=[CH:45][CH:44]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[C:13]([C@H:11]1[CH2:12][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C@H:9]([C:15](=[O:17])[NH:52][C:51]2[CH:50]=[CH:49][C:48]([O:47][C:46]3[CH:55]=[CH:56][C:43]([F:42])=[CH:44][CH:45]=3)=[CH:54][CH:53]=2)[CH2:10]1)#[N:14]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
Step (a) A flask was charged with (2S,4R)-1-(tert-butoxycarbonyl)-4-cyanopyrrolidine-2-carboxylic acid (1.0 g, 4.16 mmol), HATU (1.74 g, 4.58 mmol), 4-(4-fluorophenoxy)aniline (0.844 g, 4.16 mmol), DIEA (4.8 mL, 27 mmol) and DMF (10 mL). The reaction mixture was stirred at ambient temperature for 30 minutes and then quenched with saturated sodium bicarbonate (aq., 20 mL). The mixture was extracted with ethyl acetate (60 mL) and the extract was washed with deionized water (30 mL), and then brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to give (2S,4R)-tert-butyl 4-cyano-2-(4-(4-fluorophenoxy)phenylcarbamoyl)pyrrolidine-1-carboxylate. The crude mixture was used without further purification.
Workup
- customquenched with saturated sodium bicarbonate (aq., 20 mL)
- extractionThe mixture was extracted with ethyl acetate (60 mL)
- washthe extract was washed with deionized water (30 mL)
- dry with materialbrine (30 mL), dried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-db8633210bf44aaa893b0fc5e7e8611d
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08791102B2
Reaction notes
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