Hydrochloric Acid → 3-(2-Fluoro-4-methoxyphenyl)-1-methyl-6-trifluoromethyluracil

HRID 1608922Notes

Reaction equation

HRID 1608922 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[N:12]1[C:17](=[O:18])[CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[NH:14][C:13]1=[O:23].[CH3:24]I.Cl>CN(C)C=O>[F:3][C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[N:12]1[C:17](=[O:18])[CH:16]=[C:15]([C:19]([F:20])([F:21])[F:22])[N:14]([CH3:24])[C:13]1=[O:23]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 200830763-(2-Fluoro-4-methoxyphenyl)-6-trifluoromethyluracil

Product 1

HCID 200830733-(2-Fluoro-4-methoxyphenyl)-1-methyl-6-trifluoromethyluracilYield 72.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A mixture of 0.7 gram (0.017 mole) of sodium hydride (60% in mineral oil) in 30 mL of N,N-dimethylformamide was stirred, and a solution of 5.1 grams (0.017 mole) of 3-(2-fluoro-4-methoxyphenyl)-6-trifluoromethyluracil in 35 mL of N,N-dimethylformamide was added dropwise. The reaction mixture was then stirred for about 30 minutes, and a solution of 3.8 grams (0.017 mole) of methyl iodide in 35 mL of N,N-dimethylformamide was added dropwise. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 18 hours. After this time the reaction mixture was poured into an aqueous solution of 0.25N hydrochloric acid, and the mixture was extracted with diethyl ether. The ether extract was washed with an aqueous solution of 0.25N hydrochloric acid, water, and then with an aqueous solution saturated with sodium chloride. The organic layer was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel. Elution was accomplished using 1:1 ethyl acetate in heptane. The product-containing fractions were combined and concentrated under reduced pressure, yielding 3.9 grams of 3-(2-fluoro-4-methoxyphenyl)-1-methyl-6-trifluoromethyluracil. The NMR spectrum was consistent with the proposed structure.

Workup

  1. stirringThe reaction mixture was then stirred for about 30 minutes
  2. additionUpon completion of addition
  3. stirringthe reaction mixture was stirred at ambient temperature for about 18 hours
  4. extractionthe mixture was extracted with diethyl ether
  5. extractionThe ether extract
  6. washwas washed with an aqueous solution of 0.25N hydrochloric acid, water
  7. concentrationThe organic layer was concentrated under reduced pressure to a residue
  8. washElution
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-73a26c4cdab3444b9e6ebc35a93411e1
Source dataset
uspto-grants-1995_03
Patent number
US05399543

Reaction notes

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