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

HRID 1192631Notes

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.[O:24]([CH:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH: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:34]2[CH2:35][CH2:36][CH:31]([O:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:32][CH2:33]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 (0.12 g, 0.34 mmol, from Example 47, Step 2), 4-phenoxypiperidine hydrochloride (0.087 g, 0.41 mmol), palladium acetate (1.5 mg, 0.0067 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6.3 g, 0.010 mmol), and cesium carbonate (0.42 g, 1.3 mmol) in tetrahydrofuran (4 mL) was heated at 65° C. overnight. The mixture was cooled, diluted with dichloromethane and filtered. The filtrate was washed with brine, dried over MgSO4, evaporated and purified on silica gel (eluting with 100% dichloromethane) to give the desired product (23.6 mg, 18%). LCMS calculated for C22H22ClN2O2 (M+H)+: m/z=380.1; Found: 381.1.

Workup

temperatureThe mixture was cooled
filtrationfiltered
washThe filtrate was washed with brine
dry with materialdried over MgSO4
customevaporated
custompurified on silica gel (eluting with 100% dichloromethane)

Sources & evidence

ORD record: ord-c4a2645b99f5413d886967fb82ac0001
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680108B2

Reaction notes

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