2-Chloropyrimidine-4-carboxylic acid synthesis

Yield:149849-92-3 80.8%

Reaction Conditions:

with N-hydroxyphthalimide;diethylene glycol dimethyl ether;oxygen;cobalt(II) acetate;manganese(II) acetate in acetic acid at 130; for 2 h;Reagent/catalyst;Temperature;

Steps:

1.2; 11.2; 12.2; 13.2; 14.2; 15.2; 16.2; 17.2; 18; 19 Step2 continuous oxidation reaction:
Compound C 828.7g (1.0equiv.),Catalyst Co (OAc) 2 80.3g (5% mol compound C),Catalyst Mn (OAc) 2 79g (5% mol compound C),Additive NHPI 105.1g (10% mol compound C),Additive DMG 60.3g (10% mol Compound C)It was dissolved in 10V acetic acid to form a second raw material liquid. Pump 3 is used to pump the second raw material liquid into the coil at a speed of 18.2 g / min.At the same time, 618 g (3.0 equiv.) Of oxygen was added to the coil at a rate of 1405 mL / min through a gas flow meter to perform a continuous oxidation reaction.The coil was placed in an external bath at 130 ° C.The retention time of the second raw material liquid in the coil is 2h.The discharge port is connected to the receiving device.The oxidation reaction solution in the receiving device is concentrated to 4V, the temperature is lowered to 20-25 ° C, the temperature is maintained for 2 hours, and the crystal is filtered.827.7 g (2-chloropyrimidine-4-carboxylic acid) was obtained as a white solid product,The yield was 80.8%.

References:

Tianjin Kailaiying Pharmaceutical Co., Ltd.;Hong Hao;Lu Jiangping;Zhang Enxuan;Wei Fuliang;Yang Sihang CN110642789, 2020, A Location in patent:Paragraph 0045-0046; 0056-0063

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