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ChemicalBook CAS DataBase List 7-AMCA
24701-69-7

7-AMCA synthesis

10synthesis methods
-

Yield: 43 g

Reaction Conditions:

Stage #1:7-Aminocephalosporanic acid with 1H-imidazole;1,1,1,3,3,3-hexamethyl-disilazane in dimethyl sulfoxide at 30 - 35; for 1 h;Inert atmosphere;
Stage #2:Trimethyl borate with methanesulfonic acid in methanol;dimethyl sulfoxide at 0 - 5;Concentration;Solvent;Reagent/catalyst;

Steps:

6 Example 6:
Under nitrogen protection,In the reaction flask was added 360ml dimethyl sulfoxide,60 g (0.22 mol) 7-ACA was added,Temperature control at 30-35 ,Imidazole 0.8g,3.55 g (0.022 mol) of hexamethyldisilazane,After stirring for 60 minutes,Evacuated for 30 minutes to remove the ammonia produced,Then cooled to 0-5 ,25.15 g (0.242 mol) of trimethyl borate,8.11 g (0.253 mol) of methanol,An additional 317.1 g (3.3 mol) of methanesulfonic acid,25.15 g (0.242 mol) of trimethyl borate and 8.11 g (0.253 mol)Methanol mixture,Feeding time 60min;After adding,Temperature control at 0-5 ,Reaction 2 to 3 hours;2 hours after sampling,7-ACA residual test,HPLC peak area normalization method ≤ 0.5%The system was cooled to -10 ;Good cooling 90ml cold water (0 ~ 3 ) dripped into the system,Dropping is completed,Temperature 0-5 ,Stir for 30min,filter,The filtrate is transferred to a crystallization flask;Filter cake without washing,Drained to recover solids,After the filtrate was decolorized with activated carbon,0 ~ 5 with a good pre-5% aqueous ammonia solution was added to the system,Adjust pH = 3.0-3.5, 0 ~ 5 Yangjing 60min,Wash with 100 ml of cold water (0-3 ° C)Cold methanol (0 ~ 3 ° C) 100ml wash,Drying 40 vacuum drying,43g (0.176 mol) of a white solid, 7-AMCA,Yield 0.80;Quality Index:HPLC 99.2%, D-7-ACA 0.15%, 7-ADCA 0.20%, 7-ACA lactone 0.18%, 7-ACA 0.06%The largest unknown singlet 0.18%.

References:

Hubei Lingsheng Pharmaceutical Co., Ltd.;Men Wanhui;Jin Lianming CN106478666, 2017, A Location in patent:Paragraph 0025; 0026; 0027; 0028; 0029; 0030; 0031; 0032

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