Sodium hydride → HCID 22404793, compound

HRID 440663Notes

Reaction equation

HRID 440663 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[C:22](=[O:27])[C:23]([CH3:26])([CH3:25])[O:24][C:20]=2[C:19]([N:28]=[C:29]=[O:30])=[C:18]([Cl:31])[CH:17]=1>O1CCCC1.O>[Cl:15][C:16]1[C:21]2[C:22](=[O:27])[C:23]([CH3:26])([CH3:25])[O:24][C:20]=2[C:19]([N:28]2[C:6](=[O:8])[CH:5]=[C:4]([C:11]([F:12])([F:13])[F:14])[NH:3][C:29]2=[O:30])=[C:18]([Cl:31])[CH:17]=1

Participants

6

Reactant 3

HCID 24758Sodium hydride2×HCID 5702529Ethyl 3-amino-4,4,4-trifluorocrotonateHCID 22404734HCID 22404734, compound

Product 1

HCID 22404793HCID 22404793, compoundYield 72.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A 60% dispersion of sodium hydride in mineral oil (0.78 g, 0.019 mole) was placed in a flask, and the mineral oil was removed from it with two heptane washes. The sodium hydride was suspended in 40 mL of dry tetrahydrofuran, and this suspension was cooled to 0°-10° C. A solution of 2.96 g (0.0162 mole) of ethyl 3-amino-4,4,4-trifluorocrotonate in 5 mL of dry tetrahydrofuran was added dropwise to the suspension of sodium hydride. This mixture was then stirred at ambient temperature for 30 minutes. A solution of 4.40 g (0.0162 mole) of 4,6-dichloro-2,3-dihydro-2,2-dimethyl-benzofuran-3-on-7-yl isocyanate in 10 mL of dry tetrahydrofuran was added dropwise. Upon completion of addition, the reaction mixture was stirred at ambient temperature for 30 minutes and then was heated at reflux for three hours. At the conclusion of this period the mixture was diluted with water, and the resulting mixture was extracted three times with ethyl acetate. The combined extracts were dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated under reduced pressure, yielding 9.58 g of a gummy, pale yellow residue. This residue was triturated with methylene chloride, yielding 4.79 g of 3-(4,6-dichloro-2,3-dihydro-2,2-dimethylbenzofuran-3-on-7-yl)-6-trifluoromethyluracil as an off-white solid, m.p. 308°-320° C. The NMR and IR spectra were consistent with the proposed structure.

Workup

  1. customthe mineral oil was removed from it with two heptane washes
  2. temperaturethis suspension was cooled to 0°-10° C
  3. additionUpon completion of addition
  4. stirringthe reaction mixture was stirred at ambient temperature for 30 minutes
  5. temperaturewas heated
  6. temperatureat reflux for three hours
  7. extractionthe resulting mixture was extracted three times with ethyl acetate
  8. dry with materialThe combined extracts were dried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customthe filtrate was evaporated under reduced pressure
  11. customyielding 9.58 g of a gummy, pale yellow residue
  12. customThis residue was triturated with methylene chloride

Sources & evidence

ORD record
ord-3a77ea2c233f462da82b6db55934f601
Source dataset
uspto-grants-1996_05
Patent number
US05521147

Reaction notes

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