Cesium carbonate → 1-(4-Chloro-5,7-difluoro-3-methylquinolin-2-yl)-5,5-dimethylpiperidin-2-one
Reaction equation
C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.Cl[C:44]1[C:53]([CH3:54])=[C:52]([Cl:55])[C:51]2[C:46](=[CH:47][C:48]([F:57])=[CH:49][C:50]=2[F:56])[N:45]=1.[CH3:58][C:59]1([CH3:66])[CH2:64][NH:63][C:62](=[O:65])[CH2:61][CH2:60]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CCOC(C)=O.C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:55][C:52]1[C:51]2[C:46](=[CH:47][C:48]([F:57])=[CH:49][C:50]=2[F:56])[N:45]=[C:44]([N:63]2[CH2:64][C:59]([CH3:66])([CH3:58])[CH2:60][CH2:61][C:62]2=[O:65])[C:53]=1[CH3:54]Participants
9
Reactant 4
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 100 °C
Procedure
The 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (273 mg, 0.472 mmol), 2,4-dichloro-5,7-difluoro-3-methylquinoline (XantPhos) (780 mg, 3.20 mmol), 5,5-dimethylpiperidin-2-one (400 mg, 3.20 mmol), cesium carbonate (1.40 g, 4.40 mmol) and Pd2(dba)3 (140 mg, 0.160 mmol) were slurried in 1,4-dioxane (8.5 mL) and heated in a microwave reactor at 100° C. for 3 h. The reaction was cooled and then diluted with EtOAc and DCM. The slurry was then filtered and the filtrate cond. The residue was purified by medium pressure chromatography (silica gel, 0 to 50% EtOAc:DCM) to give 1-(4-chloro-5,7-difluoro-3-methylquinolin-2-yl)-5,5-dimethylpiperidin-2-one. Mass Spectrum (ESI) m/e=339.1 (M+1).
Workup
- temperatureThe reaction was cooled
- filtrationThe slurry was then filtered
- customThe residue was purified by medium pressure chromatography (silica gel, 0 to 50% EtOAc:DCM)
Sources & evidence
- ORD record
- ord-f3939e7995144f169ebeddba726f907e
- Source dataset
- uspto-grants-2015_01
- Patent number
- US08940724B2
Reaction notes
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