Acetone → 6-Chloro-2-fluoro-3-(methoxymethoxy)pyridine

HRID 931545Notes

Reaction equation

HRID 931545 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([F:8])[C:5]([OH:9])=[CH:4][CH:3]=1.[C:10]([O-:13])([O-])=O.[K+].[K+].[CH3:16]C(C)=O>>[Cl:1][C:2]1[N:7]=[C:6]([F:8])[C:5]([O:9][CH2:16][O:13][CH3:10])=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 180AcetoneHCID 11430Potassium CarbonateHCID 574756406-Chloro-2-fluoropyridin-3-ol

Product 1

HCID 574756416-Chloro-2-fluoro-3-(methoxymethoxy)pyridineYield 80%

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 MOMC1 (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-f9b58a0d451143c4860f2ab3100c82a2
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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