1,4-Dioxane → HCID 59398215, compound

HRID 2193113Notes

Reaction equation

HRID 2193113 reaction equation
O1CCOCC1.Cl[C:8]1[C:13]([CH2:14][O:15][CH2:16][O:17][CH3:18])=[CH:12][C:11]([F:19])=[C:10]([CH3:20])[N:9]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C.O.C(O)=O.C(N(CC)CC)C.CN(C)C=O>[F:19][C:11]1[C:10]([CH3:20])=[N:9][CH:8]=[C:13]([CH2:14][O:15][CH2:16][O:17][CH3:18])[CH:12]=1

Participants

9

Reactant 2

HCID 312751,4-DioxaneHCID 59398303HCID 59398303, compound

Product 1

HCID 59398215HCID 59398215, compound

Reagents, catalysts & solvents 6

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 284Formic AcidSolvent2×HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To 30 mL of a 1,4-dioxane solution containing 2.4 g of 2-chloro-5-fluoro-3-((methoxymethoxy)methyl)-6-methylpyridine, 2.3 mL of triethylamine, 0.61 mL of formic acid and 0.63 g of tetrakis(triphenylphosphine)palladium(0) were added, and the mixture was stirred for 2 hours with reflux by heating under a nitrogen atmosphere. Thereto was added 30 mL of N,N-dimethylformamide, and the mixture was stirred at 90 to 100° C. for 1 hour. Thereto were added 2.3 mL of triethylamine, 0.61 mL of formic acid and 0.63 g of tetrakis(triphenylphosphine)palladium(0), and the mixture was stirred at 90 to 100° C. for 1 hour. Water and ethyl acetate were added thereto, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, and the resultant solution was 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 flash silica gel column chromatography [hexane:gradient elution of ethyl acetate=95:5 to 80:20] to obtain 1.8 g of a yellow oily substance, 3-fluoro-5-((methoxymethoxy)methyl)-2-methylpyridine.

Workup

  1. additionwere added
  2. temperaturewith reflux
  3. temperatureby heating under a nitrogen atmosphere
  4. stirringthe mixture was stirred at 90 to 100° C. for 1 hour
  5. stirringthe mixture was stirred at 90 to 100° C. for 1 hour
  6. customthe organic layer was separated
  7. extractionthe aqueous layer was extracted with ethyl acetate
  8. washthe resultant solution was washed sequentially with water
  9. dry with materialan aqueous saturated sodium chloride solution, and dried over anhydrous magnesium sulfate
  10. customthe solvent was removed under reduced pressure
  11. customThe residue thus obtained
  12. customwas purified by flash silica gel column chromatography [hexane:gradient elution of ethyl acetate=95:5 to 80:20]

Sources & evidence

ORD record
ord-4685fcd0bbcb4c9eb45a25124c06da59
Source dataset
uspto-grants-2012_12
Patent number
US08329694B2

Reaction notes

Loading…