Cefathiamidine Impurity 4 synthesis

Yield:28307-26-8 93.6%

Reaction Conditions:

Stage #1: 7-Aminocephalosporanic acidwith sodium hydrogencarbonate in water at 0 - 35;
Stage #2: dichloroacethyl chloride in water at 0 - 5; for 0.5 h;Reagent/catalyst;

Steps:

1

(1) 10g of 7-ACA raw material was added to 100ml of water,Then add 9.25g sodium bicarbonate,30 ~ 35 under stirring for 1 ~ 2h dissolved,Cooled to 0 ~ 5 ,Temperature control dropping 8.14g dichloroacetyl chloride,After maintaining the reaction at 0 ~ 5 for 30min, the solution was adjusted to pH4.5 ~ 5.0 with 30wt% sodium hydroxide,0 ~ 5 Yang Jing 2 hours, filtered, the filter cake was washed with 15ml,The product was dried at 25-30 ° C to obtain 13.2 g of compound of formula (II)Product purity greater than 98%Molar yield: 93.6%.

References:

CN105017287,2018,B Location in patent:Paragraph 0043; 0047