Sodium Iodide → 1-[[2-Fluoro-6-(trifluoromethyl)phenyl]methyl]-6-methylpyrimidine-2,4-dione

HRID 1744300Notes

Reaction equation

HRID 1744300 reaction equation
[Na+].[I-].[F:3][C:4]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[C:5]=1[CH2:6][NH:7][C:8]([NH2:10])=[O:9].[CH2:19]=[C:20]1O[C:22](=[O:23])[CH2:21]1.C[Si](Cl)(C)C>C(#N)C.O>[F:3][C:4]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:16])([F:17])[F:18])[C:5]=1[CH2:6][N:7]1[C:20]([CH3:19])=[CH:21][C:22](=[O:23])[NH:10][C:8]1=[O:9]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 12661DiketeneHCID 22037856N-(2-Fluoro-6-(trifluoromethyl)benzyl)urea

Product 1

HCID 220378661-[[2-Fluoro-6-(trifluoromethyl)phenyl]methyl]-6-methylpyrimidine-2,4-dioneYield 81.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

NaI (43.9 g, 293 mmol) was added to N-[2-fluoro-6-(trifluoromethyl)benzyl]urea 4b (46.2 g, 19.6 mmol) in 365 mL of acetonitrile. The resulting mixture was cooled in an ice-water bath. Diketene (22.5 mL, 293 mmol) was added slowly via dropping funnel followed by addition of TMSCl (37.2 mL, 293 mmol) in the same manner. The resulting yellow suspension was allowed to warm to room temperature slowly and was stirred for 20 hours. LC-MS showed the disappearance of starting material. To the yellow mixture 525 mL of water was added and stirred overnight. After another 20 hours stirring, the precipitate was filtered via Buchnner funnel and the yellow solid was washed with water and EtOAc to give 4c as a white solid (48.5 g, 16 mmol). 1H NMR (CDCl3) δ 2.152 (s, 3H), 5.365 (s, 2H), 5.593 (s, 1H), 7.226–7.560 (m, 3H), 9.015 (s, 1H); MS (CI) m/z 303.0 (MH+).

Workup

  1. temperatureThe resulting mixture was cooled in an ice-water bath
  2. stirringstirred overnight
  3. stirringAfter another 20 hours stirring
  4. filtrationthe precipitate was filtered via Buchnner funnel
  5. washthe yellow solid was washed with water and EtOAc

Sources & evidence

ORD record
ord-8415b602d6b94be09ae5ccc103f3af75
Source dataset
uspto-grants-2006_03
Patent number
US07015226B2

Reaction notes

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