PROCESS FOR THE MANUFACTURE OF 7-BETA-ACYLAMINOCEPH-3-EM- 4-CARBOXYLIC ACID COMPOUNDS

摘要

1467407 7 - Acylamino - ceph - 3 - em - 4- carboxylic acids and derivatives thereof CIBAGEIGY AG 28 March 1974 [30 March 1973] 13720/74 Heading C2C Novel compounds of the Formula I wherein X is sulphur or oxygen, R is hydrogen or an amino protective group, R 1 is hydrogen, a free etherified or esterified hydroxyl or mercapto group, or a substituted ammonium group, R 2 is hydroxyl or a carboxyl protective radical which together with the carbonyl grouping of the formula -C(: O)- forms a protected carboxyl group, or salts thereof, may be prepared by acylating a compound of the Formula II wherein the amino group is optionally substituted by a group which permits acylation to take place, or a salt thereof with carboxylic of the Formula III or a reactive derivative thereof and optionally removing or interconverting protective groups at R and R 2 , converting R 1 groups to other R 1 groups and forming salts or free compounds. 2 - (5 - N - tert. - Butoxycarbonylaminomethyl- 2-thienyl acetic acid is prepared by reacting thenylamine hydrochloride with trifluoroacetic acid and acetic anhydride to form 2-acetyl-5- trifluoroacetylaminomethyl-thiophene which with perchloric acid, thallium nitrate and methanol yields 2 - (5 - trifluoroacetylaminomethyl - 2- thienyl) acetic acid, methyl ester which with base and then t-butoxycarbonyl azide yields the required compound. 2-(5-N-t-Butoxycarbonylamino-2-furyl) acetic acid is prepared by an analogous process from furfurylamine. 2-Acetyl- 5 - trifluoroacetylaminomethyl - thiophene is also prepared by reacting thiophene with N- hydroxymethyltrifluoroacetamide in trifluoroacetic acid and acetic anhydride. Pharmaceutical compositions of the compounds I in which R is hydrogen and R 2 is hydroxyl or a radical which together with the carbonyl grouping of the formula -C(=O)- forms an esterified carbonyl group which can be split under physiological conditions or a physiologically acceptable salt thereof, with the usual excipients show antibiotic activity when administered orally or parenterally.