Methyl iodide → HCID 19025384, compound

HRID 1033157Notes

Reaction equation

HRID 1033157 reaction equation
[H-].[Na+].[NH2:3][C:4]([C:11]([F:14])([F:13])[F:12])=[CH:5][C:6]([O:8]CC)=O.[F:15][C:16]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:17]=1[N:25]=[C:26]=[O:27].[C:28](=O)([O-])[O-].[K+].[K+].CI>O1CCCC1.O.C(OCC)C>[F:15][C:16]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:17]=1[N:25]1[C:6](=[O:8])[CH:5]=[C:4]([C:11]([F:12])([F:13])[F:14])[N:3]([CH3:28])[C:26]1=[O:27]

Participants

9

Reactant 5

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 136209Ethyl 3-amino-4,4,4-trifluoro-2-butenoateHCID 14698843HCID 14698843, compound

Product 1

HCID 19025384HCID 19025384, compoundYield 88.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

A stirred suspension of 2.7 grams (0.066 mole) of 60% sodium hydride (in mineral oil) in 125 mL of tetrahydrofuran was cooled to -20° C., and 11.0 grams (0.060 mole) of ethyl 3-amino-4,4,4-trifluoro-2-butenoate was added dropwise. Upon completion of addition, the reaction mixture was stirred for about 10 minutes, and 10.9 grams (0.060 mole) of 2-fluoro-4-nitrophenyl isocyanate was added dropwise. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature, where it was stirred for one hour. After this time the reaction mixture was warmed to reflux, where it was stirred for about 16 hours. The reaction mixture was then cooled to about ambient temperature, and 8.3 grams (0.060 mole) of potassium carbonate and 17.1 grams (0.120 mole) of methyl iodide were added. Upon completion of addition, the reaction mixture was warmed to reflux, where it was stirred for about 7 hours. The reaction mixture was cooled to ambient temperature and stirred with diethyl ether and water. The organic layer was separated, washed with water, and dried with magnesium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure to a residue. The residue was combined with a previous run (0.070 mole) of this reaction, and the mixture was subjected to column chromatography on silica gel. Elution was accomplished with heptane, 1:1 heptane-methylene chloride, and methylene chloride. The product-containing fractions were combined and concentrated under reduced pressure, yielding 17.7 grams of 3-(2-fluoro-4-nitrophenyl)-1-methyl-6-trifluoromethyluracil; mp 135°-136° C. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionUpon completion of addition
  2. additionUpon completion of addition
  3. temperatureto warm to ambient temperature
  4. stirringwhere it was stirred for one hour
  5. temperatureAfter this time the reaction mixture was warmed
  6. temperatureto reflux
  7. stirringwhere it was stirred for about 16 hours
  8. temperatureThe reaction mixture was then cooled to about ambient temperature
  9. additionUpon completion of addition
  10. temperaturethe reaction mixture was warmed
  11. temperatureto reflux
  12. stirringwhere it was stirred for about 7 hours
  13. temperatureThe reaction mixture was cooled to ambient temperature
  14. customThe organic layer was separated
  15. washwashed with water
  16. dry with materialdried with magnesium sulfate
  17. filtrationThe mixture was filtered
  18. concentrationthe filtrate was concentrated under reduced pressure to a residue
  19. customThe residue was combined with a previous run (0.070 mole) of this reaction
  20. washElution
  21. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-65e376385e43478181043b81e2487138
Source dataset
uspto-grants-1994_05
Patent number
US05310723

Reaction notes

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