Sodium Hydroxide → 4-Chloro-2-(3-chlorophenyl)-6-ethylpyrimidine
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[NH:13][C:12](=O)[CH:11]=[C:10]([CH2:15][CH3:16])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.O=P(Cl)(Cl)[Cl:19].C([O-])(O)=O.[Na+].[OH-].[Na+]>>[Cl:19][C:12]1[CH:11]=[C:10]([CH2:15][CH3:16])[N:9]=[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[N:13]=1Participants
Conditions
- Temperature
- 100 °C
Procedure
A 250-mL round bottom flask was charged with 2-(3-chlorophenyl)-6-ethylpyrimidin-4(3H)-one (9.3 g, 39.8 mmol, 1 eq.). POCl3 (50 mL, 536 mmol, 13.4 eq.) was cautiously added at 0° C. The resulting mixture was stirred at 100° C. for 5 hr. After cooling to room temperature, the mixture was added slowly dropwise to cold aq. NaHCO3. NaOH was added to keep the pH˜0.7 during quenching. The mixture was extracted with ethyl acetate. The organic extract was dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography using dichloromethane/ethyl acetate as eluent afforded 4-chloro-2-(3-chlorophenyl)-6-ethylpyrimidine (9.3 g, 99% yield) as a white solid. 1H NMR (CD3OD, 500 MHz) δ 8.32 (s, 1H), 8.28 (d, J=7.5 Hz, 1H), 7.50-7.46 (m, 1H), 7.45-7.40 (m, 1H), 7.27 (s, 1H), 2.83 (q, J=7.5 Hz, 2H), 1.34 (t, J=7.5 Hz, 3H).
Workup
- temperatureAfter cooling to room temperature
- customduring quenching
- extractionThe mixture was extracted with ethyl acetate
- extractionThe organic extract
- dry with materialwas dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customPurification by silica gel chromatography
Sources & evidence
- ORD record
- ord-b0c5a58b201d4af0971f44a04f5b87fb
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09221843B2
Reaction notes
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