Sodium hydride → 3-(4-chloro-2-nitrophenyl)-6-trifluoromethyl-2,4 (1H, 3H)-pyrimidinedione

HRID 277429

Reaction equation

HRID 277429 reaction equation
[H-].[Na+].C(O[C:6](=[O:14])/[CH:7]=[C:8](\[NH2:13])/[C:9]([F:12])([F:11])[F:10])C.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]=[C:23]=[O:24])=[C:18]([N+:25]([O-:27])=[O:26])[CH:17]=1>CN(C)C=O.C1(C)C=CC=CC=1>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[C:6](=[O:14])[CH:7]=[C:8]([C:9]([F:10])([F:11])[F:12])[NH:13][C:23]2=[O:24])=[C:18]([N+:25]([O-:27])=[O:26])[CH:17]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 42472574-Chloro-2-nitrophenyl isocyanateHCID 5702529Ethyl 3-amino-4,4,4-trifluorocrotonate

Product 1

HCID 570852913-(4-chloro-2-nitrophenyl)-6-trifluoromethyl-2,4 (1H, 3H)-pyrimidinedione

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
-30 °C

Procedure

To a suspension of sodium hydride (60% dispersion in oil, 2.5 g) in anhydrous N,N-dimethylformamide (100 ml) was added dropwise a solution of ethyl-3-amino-4,4,4-trifluorocrotonate in toluene (50 ml) at 0° C. under nitrogen atmosphere. After addition, the mixture was stirred for 20 min at same temperature, then cooled to −30° C. A solution of (4-chloro-2-nitrophenyl)isocyanate in toluene (50 ml) was added dropwise. After stirring for 20 min, the cold bath was removed and the resulting mixture was stirred overnight at ambient temperature. The reaction mixture was partitioned between ethyl acetate and 1N-hydrochloric acid. The organic phase was washed with brine (×2) and dried over anhydrous sodium sulfate. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel eluted with ethyl acetate and hexane (1:1) to afford 3-(4-chloro-2-nitrophenyl)-6-trifluoromethyl-2,4(1H, 3H)-pyrimidinedione (10.2 g) as a yellow solid.

Workup

  1. additionAfter addition
  2. stirringAfter stirring for 20 min
  3. customthe cold bath was removed
  4. stirringthe resulting mixture was stirred overnight at ambient temperature
  5. customThe reaction mixture was partitioned between ethyl acetate and 1N-hydrochloric acid
  6. washThe organic phase was washed with brine (×2)
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was removed in vacuo
  9. customthe residue was purified by column chromatography on silica gel
  10. washeluted with ethyl acetate and hexane (1:1)

Sources & evidence

ORD record
ord-b8af29faa372412783beaf9f44a95f85
Source dataset
uspto-grants-2002_03
Patent number
US06355799B1

Linked notes

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