	US 12,344,622 B2
	Refining method of midbody of latamoxef sodium
Yifeng Lu, Haikou (CN); Qin Cai, Haikou (CN); and Xingyu Chen, Haikou (CN)
Assigned to Hainan Hailing Chemipharma Corporation Ltd., Haikou (CN)
Appl. No. 17/623,252
Filed by Hainan Hailing Chemipharma Corporation Ltd., Haikou (CN)
PCT Filed Dec. 15, 2021, PCT No. PCT/CN2021/138335 § 371(c)(1), (2) Date Dec. 28, 2021, PCT Pub. No. WO2023/284247, PCT Pub. Date Jan. 19, 2023.
Claims priority of application No. 202110792892.3 (CN), filed on Jul. 14, 2021.
Prior Publication US 2024/0043449 A1, Feb. 8, 2024
Int. Cl. C07D 505/06 (2006.01); C07D 505/16 (2006.01)

CPC C07D 505/06 (2013.01) [C07D 505/16 (2013.01)]

9 Claims

1. A refining method of a midbody of latamoxef sodium with the midbody of (6R,7R)-7-Amino-7-methoxy-3-[(1-methyl-1H-tetrazol-5-ylthio)methyl]-8-oxo-5-oxa-1-aza bicyclo[4.2.0]oct-2-ene-2-carboxylic acid, the refining method comprising the following steps:

(1) dissolving (6R,7R)-7-Amino-7-methoxy-3-[(1-methyl-1H-tetrazol-5-ylthio)methyl]-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid in dichloromethane and washing with an acid solution, to divide into a dichloromethane layer and a water layer;

(2) extracting the dichloromethane layer, adding a NaHCO₃solution to stir, to divide into an organic layer and the water layer, removing the water layer by liquid separation, to leave the organic layer;

(3) stirring, crystallizing and filtering the organic layer in the step (2) in turn, to obtain a filtrate;

(4) extracting the water layer in the step (1) and adding hydrochloric acid, adjusting a pH value of 4-5 by using sodium hydroxide, performing crystal cultivation and suction filtration after performing cooling, and then performing vacuum drying under a temperature of 40-45° C., to prepare a first powder;

(5) stirring the filtrate in the step (3) under conditions of a catalyst and a normal temperature, washing with a NaCl solution and drying with anhydrous sodium sulfate, to prepare a second powder;

(6) combining the first powder and the second powder to prepare the midbody of latamoxef sodium: (6R,7R)-7-Amino-7-methoxy-3-[(1-methyl-1H-tetrazol-5-ylthio)methyl]-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; and wherein

the catalyst comprises any two of Ph₂SiH₂, RhH(CO)(PPH₃)₃and RhH(PPH₃)₄that are mixed in any proportion thereof, and a weight ratio of the catalyst to the filtrate is 0.01-0.03:1.