Sodium Iodide → 1-[[2-Fluoro-6-(trifluoromethyl)phenyl]methyl]-6-methylpyrimidine-2,4-dione
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
Reactant 4
Product 1
Reagents, catalysts & solvents 2
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
- temperatureThe resulting mixture was cooled in an ice-water bath
- stirringstirred overnight
- stirringAfter another 20 hours stirring
- filtrationthe precipitate was filtered via Buchnner funnel
- washthe yellow solid was washed with water and EtOAc
Sources & evidence
- ORD record
- ord-ad7a5804b25647659a3fd4f8ca205af2
- Source dataset
- uspto-grants-2007_06
- Patent number
- US07229995B2
Reaction notes
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