Methyl iodide → HCID 15765404, compound

HRID 2226102Notes

Reaction equation

HRID 2226102 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[O:22][C:23]([CH3:26])([CH3:25])[O:24][C:20]=2[C:19]([N:27]=[C:28]=[O:29])=[C:18]([F:30])[CH:17]=1.[C:31](=O)([O-])[O-].[K+].[K+].CI>O.O1CCCC1>[Cl:15][C:16]1[C:21]2[O: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]([CH3:31])[C:28]2=[O:29])=[C:18]([F:30])[CH:17]=1

Participants

8

Reactant 5

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 5702529Ethyl 3-amino-4,4,4-trifluorocrotonateHCID 15765403HCID 15765403, compound

Product 1

HCID 15765404HCID 15765404, compoundYield 21.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

A mixture of 0,32 g (0.0079 mole) of sodium hydride and 200 mL of dry tetrahydrofuran was cooled to -20 ° C, and 1.26 g (0.0069 mole) of ethyl 3-amino-4,4,4-trifluorocrotonate was added in a dropwise manner. This mixture was stirred for 10 minutes, and then 1.68 g (0.0069 mole) of 7-chloro-2,2-dimethyl-5-fluoro-1,3-benzodioxol-4-yl isocyanate was added in a dropwise manner. 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 0.95 g (0.0069 mole) of potassium carbonate and 1.96 g (0.0138 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, water was added to the reaction mixture, and the resulting mixture was extracted with diethyl ether. The extracts were washed with water, dried over anhydrous magnesium sulfate, filtered, and the solvent evaporated from the filtrate under reduced pressure, leaving a residue. This residue was passed through a column of silica gel, eluting with ethyl acetate:heptane (4:1). Product-containing fractions were combined, and the solvent was evaporated under reduced pressure, leaving 0.58 g of 3-(7-chloro-2,2-dimethyl-5-fluoro- 1,3-benzodioxol-4-yl)-1 -methyl-6-trifluoromethyluracil (Compound 5) as an oil. 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. stirringwas stirred for one hour
  4. temperatureAt the conclusion of this period the reaction mixture was heated to 85 ° C. at which it
  5. stirringwas stirred for approximately 16 hours
  6. temperaturewas heated at 75 ° C for seven hours
  7. extractionthe resulting mixture was extracted with diethyl ether
  8. washThe extracts were washed with water
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. customthe solvent evaporated from the filtrate under reduced pressure
  12. customleaving a residue
  13. washeluting with ethyl acetate:heptane (4:1)
  14. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-51328dacc0c54b4490df8662772d6cbd
Source dataset
uspto-grants-1994_09
Patent number
US05346881

Reaction notes

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