Abstract

Disclosed is a method for removing carboxyl and hydroxy protective groups of latamoxef. The method comprises removing the protective groups of the compound (I) under the action of hydrochloric acid and a carbocation absorbent to obtain the latamoxef acid of the formula (II), wherein R is a hydroxy protective group. The invention uses hydrochloric acid to replace trifluoroacetic acid or aluminum trichloride or tin tetrachloride, and the combination of hydrochloric acid and phenol or m-cresol requires a lower dosage, and is easier to remove, thereby avoiding the problem that trifluoroacetic acid or aluminum and tin ions remain in the final product, resulting in a final product of sub-standard quality; and the residual trace amount of hydrochloric acid forms a trace amount of sodium chloride in the post-treatment salt formation process, wherein same is harmless to the human body. Meanwhile, the method uses hydrochloric acid as an acid catalyst, such that the reaction conditions are mild and the reaction speed is fast, and thus decreasing the cost and the requirement of the production device; and the method has many advantages, such as being efficient, environmentally-friendly, economic, etc., and is suitable for industrial mass production.

IPC Classes  ?

• C07D 505/20 - Nitrogen atoms further acylated by radicals derived from carboxylic acids or by nitrogen or sulfur analogues thereof with the acylating radicals further substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• C07D 505/08 - Modification of a carboxyl group directly attached in position 2, e.g. esterification

Abstract

The present invention discloses a method for removing a carboxyl and hydroxyl protecting group of a β-lactam compound. The method is removing a carboxyl and/or hydroxyl protecting group from a protected β-lactam compound under the action of trichloroacetic acid and a carbocation absorbent to give a deprotected product of the β-lactam compound. The method of the present invention employs trichloroacetic acid instead of trifluoroacetic acid, and combines trichloroacetic acid with phenol or m-cresol, and anisole, greatly reducing the amount of trichloroacetic acid used. In addition, trichloroacetic acid is decomposed in the presence of water into chloroform and carbon dioxide in a subsequent process converting cephalosporin to a sodium salt, and is easy to remove, without the problem of residual trichloroacetic acid, achieving a high reaction yield and producing relatively few impurities. Trichloroacetic acid is cheap and environmentally friendly and is beneficial in industrial production due to cost reductions achieved.

IPC Classes  ?

• C07D 505/08 - Modification of a carboxyl group directly attached in position 2, e.g. esterification
• C07D 505/20 - Nitrogen atoms further acylated by radicals derived from carboxylic acids or by nitrogen or sulfur analogues thereof with the acylating radicals further substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• C07D 499/87 - Compounds being unsubstituted in position 3 or with substituents other than only two methyl radicals attached in position 3, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
• C07D 501/04 - Preparation from compounds already containing the ring or condensed ring systems, e.g. by dehydrogenation of the ring, by introduction, elimination or modification of substituents
• C07D 501/56 - Methylene radicals, substituted by hetero rings with the 7-amino radical acylated by carboxylic acids containing hetero rings