Yield: 96.3%

Reaction Conditions:

with tin(II) chloride dihdyrate in ethanol at 81; for 1 h;Temperature;Reagent/catalyst;Solvent;

Steps:

1-3; 1-3 Preparation of intermediate 3-amino-5-chloro-2-hydroxybenzoic acid methyl ester
(1) Dissolve 868g 5-chloro-2-hydroxy-3-nitrobenzoic acid methyl ester in 874ml ethanol,Add 4.65kg of stannous chloride hydrate and heat to reflux at 81°C for 1 hour while stirring.Use a glass rod to drop a small amount of reaction liquid on the TLC plate. If the spot is not yellow, it indicates that the reaction is complete;(2) After the reaction is complete, the reaction solution is evaporated to nearly dryness using a rotary evaporator, and ether is added in batches to wash 3 times.After drying under reduced pressure, 728 g of white solid was obtained with a yield of 96.3%.

References:

Shanghai Xinyi Vientiane Pharmaceutical Co., Ltd.;Shanghai Xinyi Yan'an Pharmaceutical Co., Ltd.;Zhang Yawen;Qian Lei;Gao Jing;Dong Jiali;Jiang Lili;Guo Jingjing;Wang Ping;Ye Zhihong;Zhang Chi;Gu Yu CN112062687, 2020, A Location in patent:Paragraph 0022-0055