Cesium carbonate → HCID 9816282, compound

HRID 1636525Notes

Reaction equation

HRID 1636525 reaction equation
O[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([CH3:12])[CH:8]=[CH:7]2.[H-].[Na+].C([O-])([O-])=[O:16].[Cs+].[Cs+].Br[C:22]([CH3:27])([CH3:26])[C:23]([NH2:25])=[O:24]>O1CCOCC1.CN1C(=O)N(C)CCC1.CN1C(=O)CCC1>[OH:16][C:22]([CH3:27])([CH3:26])[C:23]([NH:25][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([CH3:12])[CH:8]=[CH:7]2)=[O:24]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 132242-Methyl-8-hydroxyquinolineHCID 24758Sodium hydride2×HCID 1012352-Bromo-2-methylpropanamide

Product 1

HCID 9816282HCID 9816282, compoundYield 67.6%

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-hydroxyquinaldine (722 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 (50 mL), dried (Na2SO4), and concentrated to about 3 g of material. The brown oil, the rearrangement product, was chromatographed on silica (200 mL, 4 cm diam. column), eluting with 3:7 EtOAc/hexane to obtain the product as an off-white solid (610 mg, 2.50 mmol, 67.6% yield).: mp 143-144° C.: 1H NMR (300 MHz, CDCl3) δ10.99 (br s, 1 H, N--H), 8.76-8.73 (m, 1 H), 8.03 (d, 1 H, J=8.26), 7.48-7.45 (om's, 2 H), 7.32 (d, 1 H, J=9.21), 2.80 (br s, 1 H, O--H), 2.75 (s, 3 H, Ar--CH3), 1.62 (s, 6 H, C(CH3)2); 13C NMR (75 MHz, CDCl3) δ174.9, 157.4, 138.2, 136.3, 133.5, 126.2, 126.1, 122.4, 121.6, 116.3, 74.2, 28.1, 25.4; MS (CI/NH3) 245; Analysis: Calculated C 68.83, H 6.60, N 11.47; Found C 68.78, H 6.56, N 11.37.

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 (50 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated to about 3 g of material
  10. customThe brown oil, the rearrangement product, was chromatographed on silica (200 mL, 4 cm diam. column)
  11. washeluting with 3:7 EtOAc/hexane

Sources & evidence

ORD record
ord-4b84ac52608746cc8057cb7934bbede2
Source dataset
uspto-grants-2000_03
Patent number
US06034241

Reaction notes

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