Methyl iodide → 3-(4-Chloro-2,3-dihydro-2,2-dimethylbenzofuran-7-yl)-1-methyl-6-trifluoromethyluracil

HRID 440655Notes

Reaction equation

HRID 440655 reaction equation
[H-].[Na+].[NH2:3]/[C:4](/[C:11]([F:14])([F:13])[F:12])=[CH:5]\[C:6]([O:8]CC)=O.[Cl:15][C:16]1[C:21]2[CH2:22][C:23]([CH3:26])([CH3:25])[O:24][C:20]=2[C:19]([N:27]=[C:28]=[O:29])=[CH:18][CH:17]=1.[C:30](=O)([O-])[O-].[K+].[K+].CI>>[Cl:15][C:16]1[C:21]2[CH2:22][C:23]([CH3:26])([CH3:25])[O:24][C:20]=2[C:19]([N:27]2[C:6](=[O:8])[CH:5]=[C:4]([C:11]([F:12])([F:13])[F:14])[N:3]([CH3:30])[C:28]2=[O:29])=[CH:18][CH:17]=1

Participants

6

Reactant 5

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 5702529Ethyl 3-amino-4,4,4-trifluorocrotonateHCID 153462864-Chloro-2,3-dihydro-2,2-dimethylbenzofuran-7-yl isocyanate

Product 1

HCID 153462873-(4-Chloro-2,3-dihydro-2,2-dimethylbenzofuran-7-yl)-1-methyl-6-trifluoromethyluracilYield 40%

Conditions

Temperature
-20 °C

Procedure

A mixture of 0.40 g (0.01 0 mole) of sodium hydride and 1.83 g (0.10 mole) of ethyl 3-amino-4,4,4-trifluorocrotonate was cooled to -20° C. To this mixture was slowly added 2.23 g (0.01 mole) of 4-chloro-2,3-dihydro-2,2-dimethylbenzofuran-7-yl isocyanate. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature at which it was stirred for one hour. At the conclusion of this period the reaction mixture was heated to 85° C. at which it was stirred for approximately 16 hours. Then 1.38 g (0.01 mole) of potassium carbonate and 2.80 g (0.020 mole) of methyl iodide were added to the reaction mixture, and it was heated at 75° C. for seven hours. At the conclusion of this period the mixture was filtered, and the filtrate diluted with 200 mL of water. This mixture was extracted with diethyl ether. The extracts were dried over anhydrous magnesium sulfate, filtered, and the solvent evaporated from the filtrate under reduced pressure, leaving a yellow oil as residue. This oil was passed through a column of silica gel, eluting with methylene chloride:heptane (70:30). Product-containing fractions were combined, and the solvent was evaporated under reduced pressure, leaving a solid residue. This residue was washed with petroleum ether, yielding 1.50 g of 3-(4-chloro-2,3-dihydro-2,2-dimethylbenzofuran-7-yl)-1-methyl-6-trifluoromethyluracil (Compound 3), m.p. 152°-153° C. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionUpon completion of addition
  2. temperatureto warm to ambient temperature at which it
  3. temperatureAt the conclusion of this period the reaction mixture was heated to 85° C. at which it
  4. stirringwas stirred for approximately 16 hours
  5. temperaturewas heated at 75° C. for seven hours
  6. filtrationAt the conclusion of this period the mixture was filtered
  7. additionthe filtrate diluted with 200 mL of water
  8. extractionThis mixture was extracted with diethyl ether
  9. dry with materialThe extracts were dried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. customthe solvent evaporated from the filtrate under reduced pressure
  12. customleaving a yellow oil as residue
  13. washeluting with methylene chloride:heptane (70:30)
  14. customthe solvent was evaporated under reduced pressure
  15. customleaving a solid residue
  16. washThis residue was washed with petroleum ether

Sources & evidence

ORD record
ord-d4d903054ab84de9b8a478c0ebe78cbf
Source dataset
uspto-grants-1996_05
Patent number
US05521147

Reaction notes

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