Hydrochloric Acid → 3-[4-(4-Chlorophenylmethoxy)-2-fluorophenyl]-1-methyl-6-trifluoromethyluracil

HRID 1608924Notes

Reaction equation

HRID 1608924 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[N:11]([CH3:20])[C:10]1=[O:21].[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29]Cl)=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+].Cl>CN(C)C=O>[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][O:8][C:6]2[CH:5]=[CH:4][C:3]([N:9]3[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:17])([F:18])[F:19])[N:11]([CH3:20])[C:10]3=[O:21])=[C:2]([F:1])[CH:7]=2)=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 77231-Chloro-4-(chloromethyl)benzeneHCID 11430Potassium CarbonateHCID 200830773-(2-Fluoro-4-hydroxyphenyl)-1-methyl-6-trifluoromethyluracil

Product 1

HCID 152794033-[4-(4-Chlorophenylmethoxy)-2-fluorophenyl]-1-methyl-6-trifluoromethyluracilYield 81.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 0.6 gram (0.002 mole) of 3-(2-fluoro-4-hydroxyphenyl)-1-methyl-6-trifluoromethyluracil, 0.3 gram (0.002 mole) of 4-chlorophenylmethyl chloride, and 0.5 gram (0.004 mole) of potassium carbonate in 50 mL of N,N-dimethylformamide was heated at 80° C. for about 18 hours. After this time the reaction mixture was poured into aqueous 0.25N hydrochloric acid. The mixture was extracted with ethyl acetate, and the combined extracts were washed with water. The organic layer was dried with magnesium sulfate, and the mixture was filtered. The filtrate was then subjected to column chromatography on silica gel. Elution was accomplished using 1:4 heptane in ethyl acetate. The product-containing fractions were combined and concentrated under reduced pressure, yielding 0.7 gram of 3-[4-(4-chlorophenylmethoxy)-2-fluorophenyl]-1-methyl-6-trifluoromethyluracil, mp 134°-135° C. The NMR spectrum was consistent with the proposed structure.

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washthe combined extracts were washed with water
  3. dry with materialThe organic layer was dried with magnesium sulfate
  4. filtrationthe mixture was filtered
  5. washElution
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-510a08eb915343c1a8636b89fcf6cd5c
Source dataset
uspto-grants-1995_03
Patent number
US05399543

Reaction notes

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