Cesium carbonate → HCID 18970793, compound

HRID 399299Notes

Reaction equation

HRID 399299 reaction equation
O[C:2]1[CH:14]=[CH:13][C:5]2[O:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[C:4]=2[CH:3]=1.[H-].[Na+].C([O-])([O-])=[O:18].[Cs+].[Cs+].Br[C:24]([CH3:29])([CH3:28])[C:25]([NH2:27])=[O:26]>O1CCOCC1.CN1C(=O)N(C)CCC1.CN1C(=O)CCC1>[CH:3]1[C:4]2[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=3[O:6][C:5]=2[CH:13]=[CH:14][C:2]=1[NH:27][C:25](=[O:26])[C:24]([OH:18])([CH3:29])[CH3:28]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 24758Sodium hydride2×HCID 665872-DibenzofuranolHCID 1012352-Bromo-2-methylpropanamide

Product 1

HCID 18970793HCID 18970793, compoundYield 58.1%

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 2-hydroxydibenzofuran (682 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 18 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 3:7 EtOAc/hexane to obtain N-(2-dibenzofuranyl)-2-hydroxy-2-methylpropionamide as an off-white solid (580 mg, 2.15 mmol, 58.1% yield). This was recrystallized from toluene for an analytical sample: mp 134-137° C. 1H NMR (300 MHz, CDCl3) δ 8.83 (br s, 1H, N--H), 8.41 (d, 1H, C1 --H, J=2.34 Hz), 7.92 (m, 1H, Ar--H), 7.56-7.29 (om's, 5H, Ar--H), 2.46 (br s, 1H, O--H), 1.60 (s, 6H, C(CH3)2); 13C NMR (75 MHz, CDCl3) δ 174.2, 156.8, 152.9, 132.8, 127.3, 124.6, 124.2, 122.7, 120.8, 119.5, 112.0, 111.7, 74.3, 28.0; IR (KBr pellet) 1651, 1668 (amide C=O stretches), 3364 (NH stretch), 3383 (OH stretch); MS (EI) 269; Analysis: Calculated C 71.36 H 5.61 N 5.20 Found C 71.43 H 5.58 N 5.06.

Workup

  1. stirringthe resulting mixture was stirred
  2. temperatureat reflux for 18 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 3:7 EtOAc/hexane

Sources & evidence

ORD record
ord-5db3d2d384f844bda49c32009320174e
Source dataset
uspto-grants-1998_10
Patent number
US05817874

Reaction notes

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