This invention relates to a process for the preparation of amino-substituted penicillins and, more particularly, to an efficient process for producing .alpha.-aminobenzylpenicillin and related ring-substituted compounds in high yield and purity.
.alpha.-Aminobenzylpenicillin and .alpha.-amino-substituted-benzylpenicillins are well known in the art and numerous processes have been proposed for their production. In general these processes involve the reaction of 6-amino-penicillanic acid with an acylating agent such as the acid chloride, acid bromide, acid anhydride, and mixed anhydride of a derivative of .alpha.-aminophenylacetic acid or .alpha.-amino-substituted-phenylacetic acid in which the amino group is protected with a suitable protecting group.
These known methods for the preparation of .alpha.-aminobenzylpenicillins and .alpha.-amino-substituted benzylpenicillins by the acylation of 6-aminopenicillanic acid result in the preparation of mixtures which contain, in addition to the desired penicillin, unreacted starting materials, hydrolyzed acylating agent, and products of side reactions which are often difficult to separate from the desired penicillin reaction product.
Various ways have been proposed in the past to remove these unwanted materials such as, for example, the formation of insoluble arylsulfonic acid salts of .alpha.-aminobenzylpenicillin as described in U.S. Pat. No. 3,180,862, or the even more complex isolation process of U.S. Pat. No. 3,271,389, but in each case the known recovery procedures have been concentrated on removing the contaminants after the desired .alpha.-amino-substituted benzyl penicillins have been formed. Consequently, these known processes are characterized by complex procedures which at the very least increase the cost of producing the desired penicillin product.