Chloromethyl Methyl Ether → 2,6-Dichloro-3-fluoro-5-(methoxymethyl)pyridine

HRID 2193112Notes

Reaction equation

HRID 2193112 reaction equation
O1CCC[CH2:2]1.[Cl:6][C:7]1[C:12]([CH2:13][OH:14])=[CH:11][C:10]([F:15])=[C:9]([Cl:16])[N:8]=1.[H-].[Na+].COCCl>C(OCC)(=O)C.O>[Cl:16][C:9]1[C:10]([F:15])=[CH:11][C:12]([CH2:13][O:14][CH3:2])=[C:7]([Cl:6])[N:8]=1

Participants

7

Reactant 4

HCID 7864Chloromethyl Methyl EtherHCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 23114857(2,6-Dichloro-5-fluoropyridin-3-yl)methanol

Product 1

HCID 874375702,6-Dichloro-3-fluoro-5-(methoxymethyl)pyridine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 100 mL of a tetrahydrofuran solution containing 5.8 g of (2,6-dichloro-5-fluoropyridin-3-yl)methanol, 1.8 g of 60% sodium hydride and 2 mL of a tetrahydrofuran solution containing 2.4 mL of chloromethyl methyl ether were added under cooling with ice, and the mixture was stirred at room temperature for 1 hour. Water and ethyl acetate were added thereto, the organic layer was separated, washed sequentially with water and an aqueous saturated sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [eluent; hexane:ethyl acetate=8:1] to obtain 5.6 g of a colorless oily substance, 2,6-dichloro-3-fluoro-5-((methoxy)methyl)pyridine.

Workup

  1. additionwere added
  2. temperatureunder cooling with ice
  3. customthe organic layer was separated
  4. washwashed sequentially with water
  5. dry with materialan aqueous saturated sodium chloride solution, and dried over anhydrous magnesium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customThe residue thus obtained
  8. customwas purified by silica gel column chromatography [eluent; hexane:ethyl acetate=8:1]

Sources & evidence

ORD record
ord-e8c70b9f09da41b2bbcbd76cda732e1a
Source dataset
uspto-grants-2012_12
Patent number
US08329694B2

Reaction notes

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