4-Methoxybenzyl alcohol → HCID 90415859, compound

HRID 1050113Notes

Reaction equation

HRID 1050113 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][OH:10])=[CH:5][CH:4]=1.[H-].[Na+].[Br:13][C:14]1[CH:15]=[C:16]([O:21][CH2:22][CH3:23])[C:17](Cl)=[N:18][CH:19]=1>CN(C=O)C>[Br:13][C:14]1[CH:15]=[C:16]([O:21][CH2:22][CH3:23])[C:17]([O:10][CH2:9][C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[N:18][CH:19]=1

Participants

5

Reactant 3

HCID 77384-Methoxybenzyl alcoholHCID 24758Sodium hydrideHCID 713036735-Bromo-2-chloro-3-ethoxypyridine

Product 1

HCID 90415859HCID 90415859, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of (4-methoxyphenyl)methanol (16.71 g, 121 mmol) in DMF (300 mL) was added NaH (3.96 g, 165 mmol) at 0° C. dropwise. After the mixture was stirred for 30 min, 5-bromo-2-chloro-3-ethoxypyridine (26 g, 110 mmol) in DMF (100 mL) was added to above mixture and the mixture was stirred for 12 h at 80-90° C. The mixture was quenched by H2O (20 mL), extracted with DCM (400 mL×2), dried over Na2SO4, filtered, and concentrated to give the residue which was purified by column chromatography (10% EA: 90% PE, 360 g silica column). All fractions found to contain product by TLC (EA: PE=1:5, Rf=0.5) were combined and concentrated to yield a white solid of 5-bromo-3-ethoxy-2-((4-methoxybenzyl)oxy)pyridine (36 g, 74.5 mmol, 68% yield): 1H NMR (400 MHz, CD3OD) δ 7.71 (d, J=2.0 Hz, 1H), 7.36-7.31 (m, 3H), 6.89-6.87 (m, 2H), 5.27 (s, 2H), 4.05-4.00 (m, 2H) 3.77 (s, 3H), 2.37 (d, J=7.0 Hz, 3H); ES-LCMS m/z 338 (M+H).

Workup

  1. stirringthe mixture was stirred for 12 h at 80-90° C
  2. customThe mixture was quenched by H2O (20 mL)
  3. extractionextracted with DCM (400 mL×2)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the residue which
  8. customwas purified by column chromatography (10% EA: 90% PE, 360 g silica column)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-947ad5c7347d4688a4097260abab1596
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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