Phosphorus oxychloride → 4-Chloro-6-(3-chlorophenyl)-2-ethylpyrimidine

HRID 1509002Notes

Reaction equation

HRID 1509002 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([CH2:14][CH3:15])[NH:11][C:10](=O)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.O=P(Cl)(Cl)[Cl:19].C(=O)(O)[O-].[Na+]>>[Cl:19][C:10]1[CH:9]=[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[N:13]=[C:12]([CH2:14][CH3:15])[N:11]=1

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 1365098196-(3-Chlorophenyl)-2-ethyl-4(3H)-pyrimidinone

Product 1

HCID 809362194-Chloro-6-(3-chlorophenyl)-2-ethylpyrimidineYield 81%

Conditions

Temperature
85 °C

Procedure

A mixture of 6-(3-chlorophenyl)-2-ethylpyrimidin-4(3H)-one (0.240 g, 1.0 mmol) and POCl3 (5 mL) was heated to 85° C. for 6 h. After this time, the reaction was cooled, neutralized with saturated aqueous sodium bicarbonate, and extracted with methylene chloride. The combined organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by column chromatography (silica, hexanes/ethyl acetate) to afford the title compound as an off-white solid (0.210 g, 81%). MW=253.13. 1H NMR (CDCl3, 500 MHz) δ 8.10 (t, J=1.9 Hz, 1H), 7.96-7.92 (m, 1H), 7.55-7:41 (m, 3H), 3.03 (q, J=7.6 Hz, 2H), 1.55 (s, 1H), 1.42 (t, J=7.6 Hz, 3H); APCI MS m/z 254 [M+H]+.

Workup

  1. temperatureAfter this time, the reaction was cooled
  2. extractionextracted with methylene chloride
  3. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. customThe residue was purified by column chromatography (silica, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-027c68ef52654591b89be018369204f1
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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