4,5-Dichloro-2,6-dimethylpyrimidine synthesis

Yield:-

Reaction Conditions:

with trichlorophosphate in dichloromethane at 120; for 0.5 h;

Steps:

1-13 4,5-dichloro-2,6-dimethylpyrimidine (XX2)

5-Bromo-2-methylpyrimidin-4-ol (MM1) (30 g, 159 mmol) was suspended in phosphorous oxychloride (150 mL).
The reaction mixture was heated at 120 °C for 30 minutes.
The reaction mixture was cooled to ambient temperature, concentrated in vacuo and azeotroped twice with toluene.
The crude residue was diluted with EtOAc (600 mL) and cooled to 0 °C. Aqueous sodium bicarbonate (150 mL) was slowly added with stirring.
The organic layer was washed once more with sodium bicarbonate (150 mL), dried over MgSO₄, filtered and concentrated in vacuo to afford the title compound as a dark oil, which was sufficiently pure to use in the subsequent step without further purification; 4,5-dichloro-2,6-dimethylpyrimidine (XX2)
The title compound was prepared according to the protocol outlined in Example 13 for the synthesis of MM2.
XX2 was isolated as a yellow gum, and was sufficiently pure to use in the subsequent step without further purification. LRMS m/z (M+H) 177.1 found, 177.0 required.

References:

EP2714041,2016,B1 Location in patent:Paragraph 0143; 0165