Sodium Carbonate → 1-[2-(4-Hydroxymethyl-phenyl)-ethyl]-4-(5-methyl-pyridin-2-ylmethoxy)-1H-pyridin-2-one

HRID 564145Notes

Reaction equation

HRID 564145 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][N:13]([CH2:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([CH2:24][OH:25])=[CH:20][CH:19]=3)[C:12](=[O:26])[CH:11]=2)=[N:6][CH:7]=1.[C:27]([O-])([O-])=O.[Na+].[Na+].CB(O)O>O1CCOCC1>[OH:25][CH2:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][CH2:16][N:13]2[CH:14]=[CH:15][C:10]([O:9][CH2:8][C:5]3[CH:4]=[CH:3][C:2]([CH3:27])=[CH:7][N:6]=3)=[CH:11][C:12]2=[O:26])=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 139377Methylboronic AcidHCID 67007373HCID 67007373, compound

Product 1

HCID 670069761-[2-(4-Hydroxymethyl-phenyl)-ethyl]-4-(5-methyl-pyridin-2-ylmethoxy)-1H-pyridin-2-one

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To 300 mg (0.72 mmol) 4-(5-bromo-pyridin-2-ylmethoxy)-1-[2-(4-hydroxymethyl-phenyl)-ethyl]-1H-pyridin-2-one (example 12.1a) is added 25 mg (0.04 mmol) bis(triphenylphosphan)palladium(II)-chloride, 1.08 mL (2.17 mmol) 2 M aqueous Na2CO3-solution and a solution of 65 mg (1.08 mmol) methyl-boronic acid in 10 mL 1,4-dioxane/5 mL MeOH. The reaction mixture is refluxed for 48 h. The solvent is evaporated and the residue is dissolved in water/DCM. The layers are separated and the aqueous phase is extracted with DCM. The combined organic phase is dried over MgSO4, filtered and the solvent is evaporated. The residue is purified via reverse HPLC chromatography (Waters symmetry, C18; water (0.15% formic acid)/acetonitrile 95:5 to 10:90).

Workup

  1. temperatureThe reaction mixture is refluxed for 48 h
  2. customThe solvent is evaporated
  3. dissolutionthe residue is dissolved in water/DCM
  4. customThe layers are separated
  5. extractionthe aqueous phase is extracted with DCM
  6. dry with materialThe combined organic phase is dried over MgSO4
  7. filtrationfiltered
  8. customthe solvent is evaporated
  9. customThe residue is purified via reverse HPLC chromatography (Waters symmetry, C18; water (0.15% formic acid)/acetonitrile 95:5 to 10:90)

Sources & evidence

ORD record
ord-6a1e7c8f8dd5463cad1062dd26775417
Source dataset
uspto-grants-2011_11
Patent number
US08067590B2

Reaction notes

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