Singh, Janak; Kim, Oak K.; Kissick, Thomas P.; Natalie, Kenneth J.; Zhang, Bo; Crispino, Gerard A.; Springer, Dane M.; Wichtowski, John A.; Zhang, Yunhui; Goodrich, Jason; Ueda, Yasutsugu; Luh, Bing Y.; Burke, Brian D.; Brown, Matthew; Dutka, Anthony P.; Zheng, Bin; Hsieh, Dau-Ming; Humora, Michael J.; North, Jeffrey T.; Pullockaran, Anne J.; Livshits, Juliya; Swaminathan, Shankar; Gao, Zhinong; Schierling, Peter; Ermann, Peter; Perrone, Robert K.; Lai, Mei C.; Gougoutas, Jack Z.; DiMarco, John D.; Bronson, Joanne J.; Heikes, James E.; Grosso, John A.; Kronenthal, David R.; Denzel, Theodor W.; Mueller, Richard H. published their research in Organic Process Research & Development on December 31 ,2000. The article was titled 《A Practical Synthesis of an Anti-Methicillin Resistant Staphylococcus aureus Cephalosporin BMS 247243》.Computed Properties of C21H20Cl2N2O3S The article contains the following contents:
A practical synthesis of the anti-methicillin resistant Staphylococcus aureus cephem (6R-trans)-E-7-[[[[2,5-dichloro-4-[3-[(carboxymethyl)amino]-3-oxo-1-propenyl]phenyl]thio]acetyl]amino]-4-[[(2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methyl]thio]-2,6-dimethyl-1-[3-(4-methylmorpholino-4-yl)propyl]-1-pyridinium, hydroxide, inner salt (BMS-247243) was developed. A process was developed for the interchange of the iodide counterion in 4-(3-aminopropyl)-4-methylmorpholinium HCl to chloride that was essential for an efficient synthesis of the C-3 4-mercaptopyridone sidechain. Use of catalytic Bu4NCl in the reaction of a chlorocinnamide with the lithium salt of methylthioglycolate formed the Me ester of the C-7 side chain of I in high yield. Reaction with the dianion of thioglycolic acid gave an increased level of the corresponding Michael addition byproduct that led to lower quality thermodn. product I by the reverse reaction. Cephem nucleus ACLH HCl was acylated with the acid chloride of acid I in a biphasic system to circumvent the cumbersome workup involved in reactions mediated by carbodiimdes DCC or EDAC for the synthesis of the cephem diester. An unusual degradation product diacid was obtained during the deprotection of the cephem diester with TFA to amorphous diacid II. Reaction of II with the 4-mercaptopyridone methylmorpholinium reactant formed BMS 247243 in moderate yield. Alternately, an efficient coupling of the cephem diester with the 4-mercaptopyridone methylmorpholinium reactant gave crystalline diester III with minimal (<1%) contamination of the double bond isomer. Double deprotection of diester III followed by crystallization furnished the double zwitterion BMS 247243 in high yield. The results came from multiple reactions, including the reaction of (6R,7R)-Benzhydryl 7-amino-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate hydrochloride(cas: 79349-53-4Computed Properties of C21H20Cl2N2O3S)
(6R,7R)-Benzhydryl 7-amino-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate hydrochloride(cas:79349-53-4) is one of azetidine.Azetidines (azacyclobutanes) constitute a well-known class of heterocyclic compounds. Azetidine scaffold has been discovered in several natural products.Computed Properties of C21H20Cl2N2O3S Several pharmacologically important synthetic compounds also contain azetidine ring. Because of inherent ring strain, the synthesis of azetidines is a challenging endeavor.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics