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 28511ノート

反応式

HRID 28511 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

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+).

後処理

  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

出典と根拠

ORDレコード
ord-7de01f8c58674d879b094db8cc6af7f9
出典データセット
uspto-grants-2008_09
特許番号
US07419983B2

反応ノート

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