4-Methoxybenzyl alcohol → 3,5-Dimethoxy-4-(4-methoxy-benzyloxy)-pyridine

HRID 1258432Notes

Reaction equation

HRID 1258432 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([CH2:9][OH:10])=[CH:7][CH:6]=1.[H][H].Br[C:16]1[C:21]([O:22][CH3:23])=[CH:20][N:19]=[CH:18][C:17]=1[O:24][CH3:25]>CN(C=O)C>[CH3:25][O:24][C:17]1[CH:18]=[N:19][CH:20]=[C:21]([O:22][CH3:23])[C:16]=1[O:10][CH2:9][C:8]1[CH:11]=[CH:12][C:5]([O:4][CH3:3])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 77384-Methoxybenzyl alcoholHCID 24758Sodium hydrideHCID 592006524-Bromo-3,5-dimethoxypyridineHCID 178418361HCID 178418361, compound

Product 1

HCID 592006313,5-Dimethoxy-4-(4-methoxy-benzyloxy)-pyridineYield 58.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To an ice-cooled suspension of sodium hydride (60% dispersion in mineral oil, 650 mg, 16.3 mmol) in dry DMF (10 ml) was added 4-methoxybenzyl alcohol (2.24 g, 16.3 mmol) drop-wise via syringe. Vigorous evolution of hydrogen was observed and the reaction was allowed to warm to room temperature and stirred for 15 minutes. 4-Bromo-3,5-dimethoxypyridine (1.17 g, 5.41 mmol) was added and the reaction heated to 90° C. overnight. After cooling, only trace starting material could be detected by TLC analysis and the reaction was quenched with water and extracted with EtOAc. The organic layer was washed with water 3 times then brine, dried over MgSO4 and concentrated onto silica-gel under reduced pressure. The solid residue was purified by flash chromatography (silica-gel, eluted sequentially with EtOAc:hexanes, 2:1, 1:0) to give the product as a tan solid (865 mg, 58%). 1H—NMR (300 MHz, CDCl3) δ 7.96 (s, 2H), 7.33 (d, J=8.5 Hz, 2H), 6.84 (d, J=8.5 Hz, 2H), 5.11 (s, 2H), 3.89 (s, 6H), 3.78 (s, 3H). MS (ES+) m/z 276.1 (M+H+).

Workup

  1. temperaturethe reaction heated to 90° C. overnight
  2. temperatureAfter cooling
  3. customthe reaction was quenched with water
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with water 3 times
  6. dry with materialbrine, dried over MgSO4
  7. concentrationconcentrated onto silica-gel under reduced pressure
  8. customThe solid residue was purified by flash chromatography (silica-gel
  9. washeluted sequentially with EtOAc

Sources & evidence

ORD record
ord-a0e29a21fc7c4dcf9f315393c5f8ee6c
Source dataset
uspto-grants-2013_06
Patent number
US08466163B2

Reaction notes

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