Patent GB-1507184-A (GB)
Title: 1-oxapenicillin intermediates and process for their preparation
IPC: C07D265/36
Filed: 1975-06-18
Abstract: 1507184 1 - Oxapenicillin intermediates QUEENS UNIVERSITY AT KINGSTON 18 June 1975 [19 June 1974] 25989/75 Heading C2C Novel compounds of Formula II wherein A is the residue of a sulphonic acid; R stands for C 1 -C 10  alkyl R<SP>12</SP>-O- wherein Ar is a monovalent radical selected from wherein R 13 , R 2  and R 3  are each hydrogen, chloro, bromo, iodo, trifluoromethyl, phenyl, C 1 -C 10  alkyl or C 1 -C 10  alkoxy, but only one of said R 13 , R 2  and R 3  may represent phenyl; R<SP>4</SP> is hydrogen, amino, carbobenzoxyamino, phenyl, fluoro, chloro, bromo, iodo, hydroxy, C 1 -C 10  alkanoyloxy or C 1 -C 10  alkoxy: X is oxygen or sulphur; R<SP>5</SP> and R<SP>6</SP> are hydrogen, phenyl, benzyl, phenethyl or C 1 -C 10  alkyl; Z<SP>1</SP>, Z<SP>2</SP> and Z<SP>3</SP> stand for C 1 -C 10  alkyl or the Argroup; R<SP>12</SP> is 2,2,2-trichloroethyl or benzyl; and R<SP>1</SP> is hydrogen, C 1 -C 10  alkyl, benzyl, benzhydryl, C 1 -C 10  alkoxybenzyl, or 2,2,2-trichloroethyl, may be prepared by treating an oxazoline of Formula I with a sulphonic acid monohydrate. Novel compounds of Formula IIB wherein R<SP>11</SP> is or R<SP>11</SP>-NH-; R<SP>7</SP> represents (C 1 -C 10 ) alkyl; R<SP>8</SP> and R<SP>9</SP> each represent (C 1 -C 10 ) alkyl, (C 1 -C 10 ) alkylthio, benzylthio, cyclohexyl, cyclopentyl, cycloheptyl, benzyl, phenethyl, phenylpropyl, furyl, thienyl, naphthyl or Ar-; R<SP>10</SP> represents (C 1 -C 10 ) alkylamino, di-(C 1 -C 10 ) alkylamino, cycloalkylamino having from 3 to 7 carbon atoms inclusive, allylamino, diallylamino, phenyl (C 1 -C 10 ) alkylamino, morpholino, (C 1 -C 10 ) alkylmorpholino, di-(C 1 -C 10 ) alkylmorpholino, morpholino (C 1 -C 10 ) alkylamino, pyrrolidino, (C 1 -C 10 ) alkylpyrrolidino, di-(C 1 -C 10 ) alkylpyrrolidino, N,N - hexamethyleneimino, piperidino, (C 1 -C 10 ) alkylpiperidino, di- (C 1 -C 10 ) alkylpiperidino, 1,2,5,6 - tetrahydropyridino, N - (C 1 -C 10 ) alkylpiperazino, N- phenylpiperazino, N - (C 1 -C 10 ) alkyl (C 1 - C 10 ) alkylpiperazino, N - (C 1 -C 10 ) alkyl - di- (C 1 -C 10 ) alkylpiperzino, furfurylamino, tetrahydrofurfurylamino, N - (C 1 -C 10 ) alkyl - N- furfurylamino, N - alkyl - N - anilino or (C 1 -C 10 ) alkoxyanilino; Z<SP>1</SP>, Z<SP>2</SP> and Z<SP>3</SP> each represent (C 1 -C 10 ) alkyl or Ar-; and R<SP>11</SP> represents (C 1 -C 10 ) alkyl, (C 1 -C 10 ) cycloalkyl, naphthyl, benzyl, phenethyl or may be prepared by neutralizing the compound of Formula II in a homogeneous or heterogeneous system in the presence of an acid chloride of formula R<SP>11</SP>COCl. Saponification of the compound IIB yields the novel compound IIC Compounds of Formula IIA may be prepared by neutralizing the compound of Formula II to allow for rearrangement of the RCO- substituent from the 2<SP>1</SP>-position to the 3<SP>1</SP>-position. The compounds of Formulae 11A and IIC may be converted to the 1-oxapenicillin derivatives III and IIIA respectively by the Michael addition procedure. The compound of Formula II may also be brominated with N-bromosuccinimide to form a mixture of salts of Formulae XX and XXI which may be neutralized to allow rearrangement of the RCO-substituent from the 2<SP>1</SP>- position to the 3<SP>1</SP>-position to form a mixture of novel compounds of Formulae XXII and XXIII This mixture may then be cyclized by the Michael addition procedure to give a brominated oxapenicillin of Formula XXVI or may undergo further rearrangement to the oxazinone derivative XXV