Cesium carbonate → HCID 58368540, compound

HRID 1192604Notes

Reaction equation

HRID 1192604 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][CH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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>[Cl:17][C:10]1[CH:9]=[C:8]([C:18](=[O:20])[CH3:19])[C:7]([N:28]2[CH2:29][CH2:30][CH:25]([F:24])[CH2:26][CH2:27]2)=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 27591584-Fluoropiperidine hydrochlorideHCID 58368658HCID 58368658, compound

Product 1

HCID 58368540HCID 58368540, compoundYield 35%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

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-fluoropiperidine hydrochloride (0.057 g, 0.41 mmol), palladium acetate (1.5 mg, 0.0068 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6.3 mg, 0.010 mmol), and cesium carbonate (0.31 g, 0.95 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 MgSO4 and evaporated to dryness. The residue was purified on silica gel (eluting with 0 to 5% methanol in dichloromethane) to give the desired product (36.4 mg, 35%). LCMS calculated for C16H17ClFN2O (M+H)+: m/z=307.1; Found: 307.0.

Workup

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. washThe filtrate was washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated to dryness
  6. customThe residue was purified on silica gel (eluting with 0 to 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-4ebb635ffc85426b8fa9ce07aeed38e7
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

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