Cesium carbonate → (6'-Methyl-2,3'-bipyridin-5-yl)methanol

HRID 82469Notes

Reaction equation

HRID 82469 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[N:16]1[CH:21]=[C:20](B2OC(C)(C)C(C)(C)O2)[CH:19]=[CH:18][C:17]=1[CH3:31]>C1COCC1.ClCCl>[CH3:31][C:17]1[N:16]=[CH:21][C:20]([C:2]2[CH:3]=[CH:4][C:5]([CH2:8][OH:9])=[CH:6][N:7]=2)=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 64212496-Bromo-3-pyridinemethanolHCID 164142722-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

Product 1

HCID 67031985(6'-Methyl-2,3'-bipyridin-5-yl)methanol

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of (6-bromo-pyridin-3-yl)-methanol (0.614 g, 3.27 mmol) in 10 mL of THF under an atmosphere of nitrogen was added cesium carbonate (3.27 mL, 2 N aqueous, 6.53 mmol), 2-picoline-5-boronic acid pinacol ester (0.477 g, 2.18 mmol), and [1,1′-bis(diphenylphosphino)-ferrocene]dichloro-palladium(II), 1:1 complex with dichloromethane (0.178 g, 0.218 mmol). The reaction was heated at 85° C. for 1 h, cooled to rt, and diluted with dichloromethane. The organic solution was washed with water, dried over sodium sulfate, filtered, and concentrated in vacuo. The aqueous fraction was concentrated in vacuo, triturated 3× with 20% methanol in dichloromethane, and collected via filtration. The combined solids were purified via silica gel chromatography, eluting with 100% ethyl acetate to provide (6′-methyl-2,3′-bipyridin-5-yl)methanol that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 201.1 for [M+H]+.

Workup

  1. temperaturecooled to rt
  2. washThe organic solution was washed with water
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. concentrationThe aqueous fraction was concentrated in vacuo
  7. customtriturated 3× with 20% methanol in dichloromethane
  8. filtrationcollected via filtration
  9. customThe combined solids were purified via silica gel chromatography
  10. washeluting with 100% ethyl acetate

Sources & evidence

ORD record
ord-73427a7aac264955874c53cdb4953e94
Source dataset
uspto-grants-2014_09
Patent number
US08846702B2

Reaction notes

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