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

HRID 1774926Notes

Reaction equation

HRID 1774926 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-b890597b09404579bc9e570c923c9e4a
Source dataset
uspto-grants-2016_02
Patent number
US09260418B2

Reaction notes

Loading…