1-(Bromomethyl)-2-fluoro-3-(trifluoromethyl)benzene → 5-(2-chloro-3-methoxyphenyl)-1-[1-fluoro-6-(trifluoromethyl)benzyl]pyrimidine-2,4(1H,3H)-dione

HRID 28511Notes

Reaction equation

HRID 28511 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:10]1[C:11](=[O:17])[NH:12][C:13](=[O:16])[NH:14][CH:15]=1.[CH3:18][Si](C([Si](C)(C)C)C(N)=O)(C)C.[F:30][C:31]1[C:38]([C:39]([F:42])([F:41])[F:40])=[CH:37][CH:36]=[CH:35][C:32]=1CBr>C(#N)C>[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:10]1[C:11](=[O:17])[NH:12][C:13](=[O:16])[N:14]([CH2:18][C:31]2([F:30])[C:38]([C:39]([F:40])([F:41])[F:42])=[CH:37][CH:36]=[CH:35][CH2:32]2)[CH:15]=1

Participants

5

Reactant 3

HCID 27375691-(Bromomethyl)-2-fluoro-3-(trifluoromethyl)benzeneHCID 11708267BistrimethylsilylacetamidHCID 220378355-(2-chloro-3-methoxyphenyl)pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 866143135-(2-chloro-3-methoxyphenyl)-1-[1-fluoro-6-(trifluoromethyl)benzyl]pyrimidine-2,4(1H,3H)-dioneYield 88.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of 5-(2-chloro-3-methoxyphenyl)pyrimidine-2,4(1H,3H)-dione 7e (2.2 g, 8.7 mmol) in acetonitrile (25 mL) was added bis(trimethylsilyl)acetamide (4.3 mL, 17.4 mmol), and the resulting solution was refluxed for 1.5 hours. The mixture was cooled to room temperature, 2-fluoro-3-trifluoromethylbenzyl bromide (2.7 g, 10.5 mmol) was added, and reflux was resumed for 16 hours. The reaction was quenched by addition of MeOH (25 mL) and stirring for 2 hours. After concentration, the residue was purified by column chromatography on silica gel with ethyl acetate/hexanes 1/1 to afford 5-(2-chloro-3-methoxyphenyl)-1-[1-fluoro-6-(trifluoromethyl)benzyl]pyrimidine-2,4(1H,3H)-dione 7f (3.3 g, 88%) as a white solid. MS (CI) m/z 429.0, 431.0 (MH+).

Workup

  1. temperaturethe resulting solution was refluxed for 1.5 hours
  2. temperaturereflux
  3. customThe reaction was quenched by addition of MeOH (25 mL)
  4. concentrationAfter concentration
  5. customthe residue was purified by column chromatography on silica gel with ethyl acetate/hexanes 1/1

Sources & evidence

ORD record
ord-7de01f8c58674d879b094db8cc6af7f9
Source dataset
uspto-grants-2008_09
Patent number
US07419983B2

Reaction notes

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