Cesium carbonate → HCID 86683818, compound

HRID 1620326Notes

Reaction equation

HRID 1620326 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([CH2:18][CH3:19])[CH:12]=1)[CH:5]=[O:6].[O:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[N:26]1[C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:28]=[N:27]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([O:10][C:9]2[CH:8]=[CH:7][C:4]([CH:5]=[O:6])=[CH:3][C:2]=2[C:30]2[N:26]([CH:21]3[CH2:22][CH2:23][CH2:24][CH2:25][O:20]3)[N:27]=[CH:28][CH:29]=2)=[CH:12][C:13]=1[CH2:18][CH3:19]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 115872081-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86683817HCID 86683817, compound

Product 1

HCID 86683818HCID 86683818, compoundYield 49.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

3-bromo-4-(4-chloro-3-ethylphenoxy)benzaldehyde (Preparation 9, 336 mg, 1.08 mmol), 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (300 mg, 1.08 mmol) and cesium carbonate (1.05 g, 3.24 mmol) were suspended in dioxane (4 mL) and water (2 mL). The suspension was degassed 40 minutes with nitrogen then tetrakis-triphenylphosphine palladium (62 mg, 0.054 mmol) was added and the reaction mixture was heated for 18 hours at 75° C. The solution was concentrated in vacuo to a quarter of its volume then diluted with water (20 mL) and extracted by ethyl acetate (3×20 mL). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude residue was purified by silica gel column chromatography eluting with a gradient from 15% diethyl ether in heptane to 50% diethyl ether in heptane to afford the title compound as a colourless oil (218 mg, 49%).

Workup

  1. customThe suspension was degassed 40 minutes with nitrogen
  2. concentrationThe solution was concentrated in vacuo to a quarter of its volume
  3. additionthen diluted with water (20 mL)
  4. extractionextracted by ethyl acetate (3×20 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified by silica gel column chromatography
  9. washeluting with a gradient from 15% diethyl ether in heptane to 50% diethyl ether in heptane

Sources & evidence

ORD record
ord-098f27733ae14c1081d47b2ce993db2e
Source dataset
uspto-grants-2014_07
Patent number
US08772343B2

Reaction notes

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