Chloromethyl Methyl Ether → Ethyl 6-methoxymethoxymethylnicotinate

HRID 1985655Notes

Reaction equation

HRID 1985655 reaction equation
[OH:1][CH2:2][C:3]1[CH:13]=[CH:12][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][N:4]=1.[H-].[Na+].[CH3:16][O:17][CH2:18]Cl>CN(C=O)C>[CH3:16][O:17][CH2:18][O:1][CH2:2][C:3]1[CH:13]=[CH:12][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][N:4]=1

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 15045504Ethyl 6-(hydroxymethyl)pyridine-3-carboxylate

Product 1

HCID 57720708Ethyl 6-methoxymethoxymethylnicotinate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-15 °C

Procedure

Ethyl 6-hydroxymethylnicotinate (30 g, 1.65×10−1 mol) is added dropwise to a suspension of sodium hydride (8 g, 1.98×10−1 mol) in DMF (250 ml) cooled to −15° C. and maintained under a nitrogen atmosphere, and the mixture is stirred for 10 minutes and then cooled to −23° C. Chloromethyl methyl ether is then added dropwise, the mixture is stirred for 5 minutes after the end of the addition and then poured into 600 ml of ice-cold saturated NaHCO3 solution. The mixture is extracted with petroleum ether and the combined organic phases are washed with water until neutral, and then with brine and dried over Na2SO4. After filtration, the solvent is evaporated off under vacuum and the residue is distilled (P: 4.2×10−2 mb; b.p.: 120-130° C.). The title product is obtained in the form of a yellow oil (21 g), which is used in the following step without further purification.

Workup

  1. temperaturemaintained under a nitrogen atmosphere
  2. temperaturecooled to −23° C
  3. stirringthe mixture is stirred for 5 minutes
  4. additionafter the end of the addition
  5. extractionThe mixture is extracted with petroleum ether
  6. washthe combined organic phases are washed with water until neutral, and then with brine
  7. dry with materialdried over Na2SO4
  8. filtrationAfter filtration
  9. customthe solvent is evaporated off under vacuum
  10. distillationthe residue is distilled (P: 4.2×10−2 mb; b.p.: 120-130° C.)

Sources & evidence

ORD record
ord-d280860ab07b44d5aec14d3a8ed82213
Source dataset
uspto-grants-2009_06
Patent number
US07547700B2

Reaction notes

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