Hydrochloric Acid → 2-[(Z)-[1-(2-aminothiazol-4-yl)-2-chloro-2-oxo-ethylidene]amino]oxy-2-methyl-propanoic acid;hydrochloride

After cooling down a mixture of 2,000 ml of dichloromethane and 2,000 ml of diethyl ether to a temperature of 0° C. to 5° C., 55 ml of phosphorus oxychloride and 38 ml of N,N-dimethylformamide were sequentially added dropwise thereto. At the same temperature, the solution was stirred for 30 minutes, and 100 g of (Z)-2-(2-t-butoxycarbonylprop-2-oxyimino)-2-(2-aminothiazol-4-yl)acetic acid was then added thereto, followed by further stirring the resulting solution for one hour. After cooling down the stirred solution to a temperature of −15° C. to −20° C., anhydrous hydrochloric acid was introduced at a rate of 500 ml/min. to 1,000 ml/min over one hour, followed by stirring the solution. Upon this stirring, the deprotection on the carboxy group was proceeded while beginning to deposit a solid material. The solid material was filtered, washed with 100 ml of dicholoromethane, and 100 ml of diethyl ether, in sequence, and then dried in vacuo, thereby yielding 85 g (86% yield) of the title compound as a white solid. Melting point (° C.): 153-158 (decomposition); 1NMR: (δ, DMSO-d6); 1.51(s, 6H), 7.19(s, 1H).

1. temperatureAfter cooling down
2. additionwere sequentially added dropwise
3. stirringby further stirring the resulting solution for one hour
4. additionwas introduced at a rate of 500 ml/min. to 1,000 ml/min over one hour
5. stirringby stirring the solution
6. filtrationThe solid material was filtered
7. washwashed with 100 ml of dicholoromethane, and 100 ml of diethyl ether, in sequence
8. customdried in vacuo

ORD record

ord-9984f42527e149fba7649b2a232edcbd

Source dataset

uspto-grants-2001_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06277996B1