Phosphorus oxychloride → 4-Chloro-6-cyclopropyl-2-(2-trifluoromethyl-phenyl)pyrimidine

HRID 253708ノート

反応式

HRID 253708 の反応式
[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[C:16]([F:19])([F:18])[F:17])[NH:7][C:6](=O)[CH:5]=2)[CH2:3][CH2:2]1.P(Cl)(Cl)([Cl:23])=O>>[Cl:23][C:6]1[CH:5]=[C:4]([CH:1]2[CH2:3][CH2:2]2)[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]([F:19])([F:18])[F:17])[N:7]=1

参加物

3

反応物 2

HCID 24813Phosphorus oxychlorideHCID 1355815616-cyclopropyl-2-(2-trifluoromethyl-phenyl)-3H-pyrimidin-4-one

生成物 1

HCID 179793904-Chloro-6-cyclopropyl-2-(2-trifluoromethyl-phenyl)pyrimidine収率 76%

反応条件

温度
0 °C

実験手順

6-Cyclopropyl-2-(2-trifluoromethyl-phenyl)-3H-pyrimidin-4-one (12.0 g, 42.8 mmol) in phosphorous oxychloride (40 mL, 428 mmol) was heated at 75-80° C. for 1 hour. The solvent was removed by evaporation and azeotroping three times with toluene. The residue was cooled to 0° C., taken up in ethyl acetate, treated with ice chips and water. The mixture was then washed sequentially with sodium bicarbonate, water and brine, dried over sodium sulfate and concentrated. Purification by flash chromatography [SiO2, 5:95 ethyl acetate:hexanes (5:95)] provided the title compound (9.71 g, 76% yield) as a colorless oil. 1H NMR (CDCl3, 500 MHz) δ 1.12 (m, 2H), 1.30 (m, 2H). 2.02 (m, 1H), 7.24 (s, 1H), 7.56 (t, J=7.6 Hz, 1H), 7.64 (t, J=7.6 Hz, 1H), 7.79 (m, 2H) ppm; MS (FIA) 299.1/300.9 (M+H); Rt (Method A) 3.882 minutes.

後処理

  1. customThe solvent was removed by evaporation
  2. customazeotroping three times with toluene
  3. additiontreated with ice chips and water
  4. washThe mixture was then washed sequentially with sodium bicarbonate, water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customPurification by flash chromatography [SiO2, 5:95 ethyl acetate:hexanes (5:95)]

出典と根拠

ORDレコード
ord-a3f896e5da9e4e769e668d5752632337
出典データセット
uspto-grants-2011_01
特許番号
US07872129B2

反応ノート

読み込み中…