8-Hydroxyquinoline → 8-Aminoquinoline

HRID 1636523Notes

Reaction equation

HRID 1636523 reaction equation
O[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[H-].[Na+].C([O-])([O-])=O.[Cs+].[Cs+].BrC(C)(C)C([NH2:24])=O>O1CCOCC1.CN1C(=O)N(C)CCC1.CN1C(=O)CCC1>[NH2:24][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2

Participants

8

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 24758Sodium hydride2×HCID 1012352-Bromo-2-methylpropanamide

Product 1

HCID 113598-AminoquinolineYield 41.4%

Reagents, catalysts & solvents 3

HCID 13387N-methyl-2-pyrrolidoneSolventHCID 312751,4-DioxaneSolventHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Procedure

To a solution of 8-hydroxyquinoline (537 mg, 3.70 mmol) in dioxane (20 mL) was added NaH (Aldrich, dry, 300 mg, 12.2 mmol) and Cs2CO3 (4.00 g, 12.2 mmol). The resulting mixture was stirred at room temperature for about 30 minutes, then 2-bromo-2-methyl-propanamide (2.03 g, 12.2 mmol) was added and the resulting mixture was stirred at reflux for 16 h. After the reflux period, NMP (20 mL), DMPU (2 mL), and NaH (Aldrich, dry, 100 mg, 4.07 mmol) were added. The resulting mixture was stirred at 150° C. for 72 h. The reaction was cooled to room temp., and partitioned between water (50 mL) and EtOAc (100 mL). The aqueous layer was extracted with EtOAc (100 mL) and the combined organics washed with water (2×50 mL), dried (Na2SO4), and concentrated to about 3 g of material. The brown oil was chromatographed on silica (200 mL, 4 cm diam. column), eluting with 30:70:1 EtOAc/hexane/NEt3 to obtain 8-aminoquinoline as an off-white solid (220 mg, 1.53 mmol, 41.3% yield).: mp 65-67° C. (lit. 62.5-64° C., Dewar, M. J. S. et. al., Journal of the Chemical Society, 1956, 2556 and 62.5-64° C., Richardson, A. et. al., Journal of Organic Chemistry, 1960, 25, 1138); 1H NMR (300 MHz, CDCl3) δ8.76 (dd, 1 H, J=4.23, 1.75 Hz), 8.06 (dd, 1 H, J=8.20, 1.96), 7.37-7.30 (om's, 2 H), 7.15 (dd, 1 H, J=8.01, 1.30), 6.92 (dd, 1 H, J=7.51, 1.42), 4.98 (br s, 2 H, N--H2); MS (EI) 144; Analysis: Calculated C 74.98, H 5.59, N 19.43; Found C 74.88, H 5.67, N 19.26.

Workup

  1. stirringthe resulting mixture was stirred
  2. temperatureat reflux for 16 h
  3. stirringThe resulting mixture was stirred at 150° C. for 72 h
  4. temperatureThe reaction was cooled to room temp.
  5. custompartitioned between water (50 mL) and EtOAc (100 mL)
  6. extractionThe aqueous layer was extracted with EtOAc (100 mL)
  7. washthe combined organics washed with water (2×50 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated to about 3 g of material
  10. customThe brown oil was chromatographed on silica (200 mL, 4 cm diam. column)
  11. washeluting with 30:70:1 EtOAc/hexane/NEt3

Sources & evidence

ORD record
ord-308a6e1d889e4464aed51d9cefe76285
Source dataset
uspto-grants-2000_03
Patent number
US06034241

Reaction notes

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