8-Hydroxyquinoline → Tert-butyl 4-(2-oxo-1-(pyridin-3-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

HRID 1895701Notes

Reaction equation

HRID 1895701 reaction equation
I[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[O:8]=[C:9]1[CH:14]=[C:13]([O:15][CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH:12]=[CH:11][NH:10]1.N1C2C(=CC=CC=2O)C=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.O.[Cu]I>[O:8]=[C:9]1[CH:14]=[C:13]([O:15][CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH:12]=[CH:11][N:10]1[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 707143-IodopyridineHCID 67366878Tert-butyl 4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Product 1

HCID 67367446Tert-butyl 4-(2-oxo-1-(pyridin-3-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylateYield 64%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 3-iodopyridine (287 mg, 1.400 mmol, TCI), tert-butyl 4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (206 mg, 0.7 mmol), quinolin-8-ol (40.6 mg, 0.280 mmol, Alfa Aesar), copper(I) iodide (9.49 μL, 0.280 mmol, Aldrich) and cesium carbonate (296 mg, 0.910 mmol, Aldrich) in DMSO (0.8 mL) was heated at 125° C. for 3 hrs. The reaction mixture was diluted with EtOAC and water and filtrated. The filtrate was separated and the aqueous layer was extracted further with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (0-10% MeOH/CH2Cl2) to give the title compound (165.7 mg, 64%) as a yellow solid. MS (ESI) 372 (M+H).

Workup

  1. filtrationfiltrated
  2. customThe filtrate was separated
  3. extractionthe aqueous layer was extracted further with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. customevaporated under reduced pressure
  7. customThe residue was purified by flash chromatography on silica gel (0-10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-931213e7ba524831a2bff3e19c927ff0
Source dataset
uspto-grants-2013_08
Patent number
US08513424B2

Reaction notes

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