Cesium carbonate → Ethyl 2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanoate

HRID 1183946Notes

Reaction equation

HRID 1183946 reaction equation
Br[CH2:2][CH2:3][C:4]([CH3:14])([S:10]([CH3:13])(=[O:12])=[O:11])[C:5]([O:7][CH2:8][CH3:9])=[O:6].[C:15]1([C:21]2[CH:26]=[CH:25][N:24]=[C:23]([OH:27])[CH:22]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.C(OCC)(=O)C.O>[CH3:14][C:4]([S:10]([CH3:13])(=[O:12])=[O:11])([CH2:3][CH2:2][N:24]1[CH:25]=[CH:26][C:21]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)=[CH:22][C:23]1=[O:27])[C:5]([O:7][CH2:8][CH3:9])=[O:6]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 5987864-Phenylpyridin-2-olHCID 86670634Ethyl 4-bromo-2-methyl-2-(methylsulfonyl)butanoate

Product 1

HCID 70817667Ethyl 2-methyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanoateYield 61.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

Ethyl 4-bromo-2-methyl-2-(methylsulfonyl)butanoate (25.02 g, 87.1 mmol) was added to a mixture of 4-phenylpyridin-2-ol (12.40 g, 72.43 mmol) and cesium carbonate (49.70 g, 152.5 mmol) in THF (150 mL). The reaction was stirred and heated at 60° C. overnight. The reaction was diluted with ethyl acetate (200 mL) and water (200 mL); the organics were separated and the aqueous layer was extracted with ethyl acetate (2×150 mL). The combined organics were dried (MgSO4), filtered, and concentrated to afford a crude solid. The crude was purified via flash chromatography using an Analogix SF65-400 g column and eluted with ethyl acetate in heptane (30-80%) to afford the title compound as a white solid (16.79 g, 61.4%). LC-MS m/z 378.6 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.31 (t, J=7.12 Hz, 3H) 1.58 (s, 2H) 2.41-2.62 (m, 2H) 3.09 (s, 3H) 3.90-4.01 (m, 1H) 4.20-4.32 (m, 3H) 6.40-6.45 (m, 1H) 6.73 (d, J=1.56 Hz, 1H) 7.31 (d, J=7.03 Hz, 1H) 7.37-7.46 (m, 2H) 7.50-7.55 (m, 2H).

Workup

  1. customthe organics were separated
  2. extractionthe aqueous layer was extracted with ethyl acetate (2×150 mL)
  3. dry with materialThe combined organics were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford a crude solid
  7. customThe crude was purified via flash chromatography
  8. washeluted with ethyl acetate in heptane (30-80%)

Sources & evidence

ORD record
ord-d369dbeb97e94425b3a2a9e0dc50e629
Source dataset
uspto-grants-2014_03
Patent number
US08664401B2

Reaction notes

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