Cesium carbonate → 1-[5-Chloro-8-(4,4-difluoropiperidin-1-yl)quinolin-7-yl]ethanone

HRID 1192551Notes

Reaction equation

FC(F)(F)S(O[C:7]1[C:8]([C:18](=[O:20])[CH3:19])=[CH:9][C:10]([Cl:17])=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)(=O)=O.Cl.[F:24][C:25]1([F:31])[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:17][C:10]1[CH:9]=[C:8]([C:18](=[O:20])[CH3:19])[C:7]([N:28]2[CH2:29][CH2:30][C:25]([F:31])([F:24])[CH2:26][CH2:27]2)=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2

Participants

Conditions

Temperature: 65 °C

Procedure

A stirred mixture of 7-acetyl-5-chloroquinolin-8-yl trifluoromethanesulfonate (0.106 g, 0.301 mmol), 4,4-difluoropiperidine hydrochloride (0.0570 g, 0.362 mmol), palladium acetate (1 mg, 0.006 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6 mg, 0.009 mmol), and cesium carbonate (0.274 g, 0.843 mmol) in tetrahydrofuran (3 mL) was heated at 65° C. overnight. The mixture was cooled, diluted with dichloromethane and filtered. The filtrate was washed with brine, dried over sodium sulfate and evaporated to dryness. The resulting residue was purified on silica gel, eluting with 0 to 50% ethyl acetate in hexane, to give the desired product. LCMS calculated for C16H16ClF2N2O (M+H)+: m/z=325.1; Found: 325.0.

Workup

temperatureThe mixture was cooled
filtrationfiltered
washThe filtrate was washed with brine
dry with materialdried over sodium sulfate
customevaporated to dryness
customThe resulting residue was purified on silica gel
washeluting with 0 to 50% ethyl acetate in hexane

Sources & evidence

ORD record: ord-f5ea403c5a8f4aa2b2404dc0385ba3c7
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680108B2

Reaction notes

Loading…