Triethylamine → 2-(4-(1,3-Dioxoisoindolin-2-yloxy)piperidin-1-yl)-2-(4-(trifluoromethoxy)phenyl)acetonitrile
Reaction equation
[F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1.P([C:22]#[N:23])(=O)(OCC)OCC.Cl.[NH:25]1[CH2:30][CH2:29][CH:28]([O:31][N:32]2[C:40](=[O:41])[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[C:33]2=[O:42])[CH2:27][CH2:26]1.C(N(CC)CC)C>O1CCCC1>[O:41]=[C:40]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:33](=[O:42])[N:32]1[O:31][CH:28]1[CH2:29][CH2:30][N:25]([CH:8]([C:7]2[CH:10]=[CH:11][C:4]([O:3][C:2]([F:13])([F:12])[F:1])=[CH:5][CH:6]=2)[C:22]#[N:23])[CH2:26][CH2:27]1Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
4-(Trifluoromethoxy)benzaldehyde (0.342 ml, 2.39 mmol) was added to a solution of diethyl phosphorocyanidate (0.363 ml, 2.39 mmol) in tetrahydrofuran (12 ml) and stirred at room temperature for 10 minutes. A suspension of 2-(piperidin-4-yloxy)isoindoline-1,3-dione hydrochloride (564 mg, 2.00 mmol) and triethylamine (0.332 ml, 2.39 mmol) in tetrahydrofuran (6 ml) was added to the reaction mixture, and the whole was stirred at room temperature for 24 hours and at 60° C. for 17 hours. The reaction mixture was concentrated in vacuo and the residue was purified by column chromatography (ethyl acetate/hexane: 5/95 to 25/75) to give 2-(4-(1,3-dioxoisoindolin-2-yloxy)piperidin-1-yl)-2-(4-(trifluoromethoxy)phenyl)acetonitrile (261 mg, 22%).
Workup
- additionwas added to the reaction mixture
- stirringthe whole was stirred at room temperature for 24 hours and at 60° C. for 17 hours
- concentrationThe reaction mixture was concentrated in vacuo
- customthe residue was purified by column chromatography (ethyl acetate/hexane: 5/95 to 25/75)
Sources & evidence
- ORD record
- ord-587d14d2674f45499c15c61af40faecb
- Source dataset
- uspto-grants-2013_08
- Patent number
- US08518934B2
Reaction notes
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