Reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][C:12](=[O:14])[NH:11][C:10](=[O:15])[CH2:9]2)=[CH:4][C:3]=1Br.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:25][C:26]1([CH3:35])[CH2:31][CH2:30][C:29](B(O)O)=[CH:28][CH2:27]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>C1(C)C=CC=CC=1.O1CCOCC1.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][C:12](=[O:14])[NH:11][C:10](=[O:15])[CH2:9]2)=[CH:4][C:3]=1[C:29]1[CH2:30][CH2:31][C:26]([CH3:35])([CH3:25])[CH2:27][CH:28]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 80 °C
Procedure
A solution of 600 mg (2.12 mmol) of 4-(4-amino-3-bromo-phenyl)-piperidine-2,6-dione (as prepared in Example 1, step (j)) in toluene (20 mL) and dioxane (20 mL) was treated with 900 mg (4.24 mmol) of K3PO4, 424 mg (2.76 mmol) of 4,4-dimethyl-cyclohex-1-enylboronic acid, and 297 mg (0.848 mmol) of 2-(dicyclohexylphosphino)biphenyl. The mixture was degassed via sonication, placed under Ar, treated with 47.6 mg (0.212 mmol) of Pd(OAc)2, and heated to 80° C. for 2.5 h. The mixture was diluted with EtOAc (100 mL) and washed with water (2×70 mL). The aqueous layer was extracted with EtOAc (100 mL), the combined organic layers were dried (MgSO4) and concentrated in vacuo. Silica gel chromatography of the residue on a 50-g Varian MegaBond Elut SPE column with 25-50% EtOAc-hexane afforded 140 mg (21%) of the title compound as a tan solid: Mass spectrum (ESI, m/z): Calcd. for C19H24N2O2, 313.2 (M+H). found 313.1.
Workup
- customThe mixture was degassed via sonication
- washwashed with water (2×70 mL)
- extractionThe aqueous layer was extracted with EtOAc (100 mL)
- dry with materialthe combined organic layers were dried (MgSO4)
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-f36b5ca6857949a6abb49beaf1f2abbe
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08759347B2
Linked notes
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