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

HRID 253708노트

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HRID 253708 반응식
[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

참가 물질

3

반응물 2

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

생성물 1

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

반응 조건

온도
0 °C

실험 절차

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.

후처리

  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)]

출처 및 근거

ORD 기록
ord-a3f896e5da9e4e769e668d5752632337
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07872129B2

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