Cesium carbonate → 1-(4-Chloro-5,7-difluoro-3-methylquinolin-2-yl)-5,5-dimethylpiperidin-2-one

HRID 1618749Notes

Reaction equation

CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.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

Conditions

Temperature: 100 °C

Procedure

XantPhos (273 mg, 0.472 mmol), 2,4-dichloro-5,7-difluoro-3-methylquinoline (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) was slurried in 1,4-dioxane (8.5 mL) and heated in a microwave reactor at 100° C. for 3 h. The reaction was cooled to rt and then diluted with EtOAc and DCM. The slurry was then filtered and concentrated. The residue was purified by column 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 to rt
filtrationThe slurry was then filtered
concentrationconcentrated
customThe residue was purified by column chromatography (silica gel, 0 to 50% EtOAc:DCM)

Sources & evidence

ORD record: ord-3af9e594ae674cc684d1e47bef10ed7a
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765940B2

Reaction notes

Loading…