Methanol → 3-(Difluoromethoxy)-2-methoxypyridine

HRID 1259333Notes

Reaction equation

HRID 1259333 reaction equation
[Na].Cl[C:3]1[C:8]([O:9][CH:10]([F:12])[F:11])=[CH:7][CH:6]=[CH:5][N:4]=1.[CH3:13][OH:14]>>[F:11][CH:10]([F:12])[O:9][C:8]1[C:3]([O:14][CH3:13])=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 887Methanol2×HCID 5360545SodiumHCID 533020352-Chloro-3-(difluoromethoxy)pyridine

Product 1

HCID 666173823-(Difluoromethoxy)-2-methoxypyridineYield 56%

Conditions

Temperature
100 °C

Procedure

As shown in step 3(a)-ii of Scheme 3(a), an excess of sodium metal was dissolved into 20 mL anhydrous methanol and 2-chloro-3-(difluoromethoxy)pyridine (2.0 g, 11.1 mmol) in anhydrous methanol was added. The reaction mixture was stirred in a sealed vessel at 100° C. for 6 hours. The volatiles were removed under reduced pressure and the residue was partitioned between EtOAc and brine. The brine was extracted with EtOAc and the combined organics were dried over Na2SO4, filtered, and the volatiles removed under reduced pressure. The product was purified by silica gel chromatography (DCM) to yield 3-(difluoromethoxy)-2-methoxypyridine as a colorless oil (Compound 2007, 1.1 g, 56% yield: ESMS (M+H) 176.

Workup

  1. additionwas added
  2. customThe volatiles were removed under reduced pressure
  3. customthe residue was partitioned between EtOAc and brine
  4. extractionThe brine was extracted with EtOAc
  5. dry with materialthe combined organics were dried over Na2SO4
  6. filtrationfiltered
  7. customthe volatiles removed under reduced pressure
  8. customThe product was purified by silica gel chromatography (DCM)

Sources & evidence

ORD record
ord-82d0206dbe104495822245adc339f530
Source dataset
uspto-grants-2013_06
Patent number
US08466288B2

Reaction notes

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