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

HRID 1725594Notes

Reaction equation

HRID 1725594 reaction equation
[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

Participants

3

Reactant 2

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

Product 1

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

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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)]

Sources & evidence

ORD record
ord-720b5bb934c3496ab2bd597a865dbd32
Source dataset
uspto-grants-2009_02
Patent number
US07491730B2

Reaction notes

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