Cesium carbonate → 5-Aminoquinoline

HRID 1636526Notes

Reaction equation

HRID 1636526 reaction equation
O[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N: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:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 24758Sodium hydride2×HCID 1012352-Bromo-2-methylpropanamideHCID 135441757Quinolin-5-ol

Product 1

HCID 119115-AminoquinolineYield 16.8%

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 5-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 7:3 EtOAc/hexane to obtain 5-aminoquinoline as a brown solid (90 mg, 0.62 mmol, 16.8% yield).: mp 98-100° C. (lit. 108-109° C., Akita, Y., et. al., Synthesis, 1977, 792); 1H NMR (300 MHz, CDCl3) δ8.89 (dd, 1 H, J=4.13, 2.06 Hz), 8.18 (dd, 1 H, J=8.49, 0.93), 7.60-7.48 (om's, 2 H), 7.35 (dd, 1 H, J=8.56, 4.26), 6.83 (dd, 1 H, J=7.13, 1.31), 4.21 (br s, 2 H, N--H2); 13C NMR (75 MHz, CDCl3) δ150.2, 149.1, 142.2, 130.0, 129.5, 120.1, 119.6, 118.7, 110.0; MS (CI/CH4) 145.

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 7:3 EtOAc/hexane

Sources & evidence

ORD record
ord-6d28aad04f6e43a09e58b63203f362ea
Source dataset
uspto-grants-2000_03
Patent number
US06034241

Reaction notes

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