Methyl iodide → HCID 18981050, compound

HRID 482434Notes

Reaction equation

HRID 482434 reaction equation
[H-].[Na+].[NH2:3]/[C:4](/[C:9]([F:12])([F:11])[F:10])=[CH:5]\[C:6]([O-])=[O:7].[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]=[C:22]=[O:23])=[CH:17][CH:16]=1.[C:24](=O)([O-])[O-].[K+].[K+].CI>O.C(OCC)C>[CH3:24][N:3]1[C:4]([C:9]([F:12])([F:11])[F:10])=[CH:5][C:6](=[O:7])[N:21]([C:18]2[CH:17]=[CH:16][C:15]([O:14][CH3:13])=[CH:20][CH:19]=2)[C:22]1=[O:23]

Participants

8

Reactant 5

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 794431-Isocyanato-4-methoxybenzeneHCID 18465963HCID 18465963, compound

Product 1

HCID 18981050HCID 18981050, compoundYield 43.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
-20 °C

Procedure

In a flask was placed 8.27 g (0.207 mole) of a 60% suspension of sodium hydride in mineral oil. The mineral oil was removed by washing the sodium hydride twice with heptane. To the flask was then added 300 mL of tetrahydrofuran. This suspension was cooled to -20° C. at which it was maintained during the dropwise addition of 37.9 g (0.207 mole) of 3-amino-4,4,4-trifluorocrotonate. This mixture was allowed to stir for 10 minutes before the dropwise addition of 30.83 g (0.207 mole) of 4-methoxyphenyl isocyanate was commenced. Upon completion of addition, the reaction mixture was heated at reflux for approximately 16 hours. At the conclusion of this period the reaction mixture was cooled to ambient temperature, and 28.56 g (0.207 mole) of potassium carbonate and 58.75 g (0.228 mole) of methyl iodide were added to it. The reaction mixture was then heated at reflux for seven hours. At the conclusion of this period the reaction mixture was cooled, and diethyl ether and water were added to it. The aqueous phase was separated from the organic phase. The latter was washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, leaving a residue. This residue was passed through a column of silica gel, eluting with ethyl acetate/heptane mixtures starting with 1:8 and concluding with 1:1. The product-containing fractions were combined, and the solvent was evaporated under reduced pressure, yielding 27.1 g of 1 -methyl-3-(4-methoxyphenyl)-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione. The NMR spectrum was consistent with the proposed structure.

Workup

  1. customIn a flask was placed
  2. customThe mineral oil was removed
  3. washby washing the sodium hydride twice with heptane
  4. additionTo the flask was then added 300 mL of tetrahydrofuran
  5. additionUpon completion of addition
  6. temperaturethe reaction mixture was heated
  7. temperatureat reflux for approximately 16 hours
  8. temperatureAt the conclusion of this period the reaction mixture was cooled to ambient temperature
  9. temperatureThe reaction mixture was then heated
  10. temperatureat reflux for seven hours
  11. temperatureAt the conclusion of this period the reaction mixture was cooled
  12. customThe aqueous phase was separated from the organic phase
  13. washThe latter was washed with water
  14. dry with materialdried over anhydrous magnesium sulfate
  15. filtrationfiltered
  16. concentrationThe filtrate was concentrated under reduced pressure
  17. customleaving a residue
  18. washeluting with ethyl acetate/heptane
  19. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-e40c4d4c2b574605ab8d6412cfb4b80d
Source dataset
uspto-grants-1998_08
Patent number
US05798316

Reaction notes

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