Chloromethyl Methyl Ether → 6-Chloro-2-fluoro-3-(methoxymethoxy)pyridine

HRID 455554Notes

Reaction equation

HRID 455554 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([F:8])[C:5]([OH:9])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH2:16](Cl)[O:17][CH3:18]>CC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([F:8])[C:5]([O:9][CH2:16][O:17][CH3:18])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 11430Potassium CarbonateHCID 574756406-Chloro-2-fluoropyridin-3-ol

Product 1

HCID 574756416-Chloro-2-fluoro-3-(methoxymethoxy)pyridineYield 82.3%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 6-chloro-2-fluoropyridin-3-ol (1.4 Kg, 9.49 mol) was dissolved in acetone (13 L), and treated with K2CO3 (1574 g, 11.39 mol, 1.2 eq) and MOMCl (840 g, 10.44 mol, 1.1 eq). The mixture was heated at 60° C. for 2 hrs. After cooling to RT, the reaction mixture was filtered to remove inorganic salts. The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography (0-10% EtOAc/hexanes), affording 6-chloro-2-fluoro-3-(methoxymethoxy)pyridine (1496 g) as a colorless oil in 80% yield over two steps.

Workup

  1. temperatureAfter cooling to RT
  2. filtrationthe reaction mixture was filtered
  3. customto remove inorganic salts
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by flash column chromatography (0-10% EtOAc/hexanes)

Sources & evidence

ORD record
ord-24d77b97b9ac422cb61dc1b27eddc73e
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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