Nitrogen → 2-chloro-5-(MethoxyMethoxy)pyridine

HRID 2387180Notes

Reaction equation

HRID 2387180 reaction equation
[H-].[Na+].N#N.[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][N:7]=1.Cl[CH2:14][O:15][CH3:16]>CN(C=O)C>[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:14][O:15][CH3:16])=[CH:8][N:7]=1

Participants

6

Reactant 4

HCID 947NitrogenHCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 8198212-Chloro-5-hydroxypyridine

Product 1

HCID 587641932-chloro-5-(MethoxyMethoxy)pyridineYield 96.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (60% dispersion in oil, 1.83 g, 46.0 mmol) was suspended in anhydrous DMF (50 mL) at under N2 at room temperature with stirring. A solution of 2-chloro-5-hydroxy-pyridine (5.0 g, 38.2 mmol) in anhydrous DMF (20 mL) was added dropwise over 30 min. Stirring at room temperature was continued for 1.5 hours. Chloromethyl methylether (3.32 mL, 44.1 mmol) was next added neat over 20 min. Stirring was continued at room temperature for 12 hours. The mixture was partitioned between water and EtOAc. The organics were washed with brine, dried over Na2SO4, filtered and concentrated. The crude residue was chromatographed on silica gel, eluting with 20% EtOAc in Hexanes to provide the desired product as a clear oil (6.4 g, 96%). 1H NMR (400 MHz, CDCl3): δ 8.18 (s, 1H), 7.36 (d, J=8.6 Hz, 1H), 7.23 (d, J=8.6 Hz, 1H), 5.19 (s, 2H), 3.50 (s, 3H).

Workup

  1. stirringStirring at room temperature
  2. stirringStirring
  3. waitwas continued at room temperature for 12 hours
  4. customThe mixture was partitioned between water and EtOAc
  5. washThe organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was chromatographed on silica gel
  10. washeluting with 20% EtOAc in Hexanes

Sources & evidence

ORD record
ord-4f0930e1b6da4fe382dfc859164b38d8
Source dataset
uspto-grants-2012_09
Patent number
US08268835B2

Reaction notes

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