Chloromethyl Methyl Ether → 2-(Benzyloxy)-5-(methoxymethoxy)pyridine

HRID 1484772Notes

Reaction equation

HRID 1484772 reaction equation
[CH2:1]([O:8][C:9]1[N:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:18][O:19][CH2:20]Cl>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][CH2:18][O:19][CH3:20])=[CH:13][N:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 425530416-(Benzyloxy)pyridin-3-ol

Product 1

HCID 672176842-(Benzyloxy)-5-(methoxymethoxy)pyridineYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
2.5 °C

Procedure

To a solution of 6-(benzyloxy)pyridin-3-ol (2.0 g, 10 mmol, 1 eq.) in DMF (20 mL) was added NaH (60% in mineral oil; 0.6 g, 15 mmol, 1.5 eq.) at 0-5° C. portion-wise. Upon the completion of addition, the mixture was continued to stir at 0-5° C. for 15 min, added chloromethyl methyl ether (0.88 g, 11 mmol, 1.1 eq.), stirred at 0-5° C. for another 20 min, and quenched with NH4Cl(sat) solution. The aqueous layer was extracted with EtOAc (3×20 mL) and the combined organic layers were washed with water and brine, dried over Na2SO4, concentrated, and purified on silica gel using 25% EtOAc/hexanes as eluent to give 2-(benzyloxy)-5-(methoxymethoxy)pyridine (2.1 g, 87%) as a colorless oil. MS (ESI) m/z 246.1 [M+H]+.

Workup

  1. additionUpon the completion of addition
  2. stirringstirred at 0-5° C. for another 20 min
  3. customquenched with NH4Cl(sat) solution
  4. extractionThe aqueous layer was extracted with EtOAc (3×20 mL)
  5. washthe combined organic layers were washed with water and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. custompurified on silica gel using 25% EtOAc/hexanes as eluent

Sources & evidence

ORD record
ord-b67882bc98c9423cb220948f069a348e
Source dataset
uspto-grants-2016_08
Patent number
US09422279B2

Reaction notes

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