7-Hydroxy-benzo[ij]quinolizine-2-carboxylic acids, intermediates, and a method for their production

Claim 1

Process for making carboxylic acids of the formula ##SPC7## wherein R 1 is hydrogen, methyl or ethyl; R 2 is methyl, ethyl, methoxy, halogen, hydroxy, nitro, amino, acetamido, or formamido; n is zero, one or two, and when n is two, R 2 may be methylenedioxy or ethylenedioxy bonded to adjacent carbon atoms; and when R 2 is ethyl, methoxy, nitro, amino, acetamido or formamido, and n is two, each R 2 must be different; which comprises the steps of: 1. reacting a alkoxyquinoline of the formula ##SPC8## wherein R 2 and n are as defined above, and alk is alkyl having 1 to 4 carbon atoms, with methyl or ethyl lithium under dry conditions in an inert solvent at a temperature between -30° and 0° C, followed by acidic hydrolytic cleavage of the alkoxy group to form a 4-oxo-1,2,3,4-tetrahydroquinoline intermediate of the formula ##SPC9## wherein R 2 and n are as defined above, and R 1 is methyl or ethyl, or alternatively, reacting a 2-anilinopropionic acid of the formula ##SPC10## wherein R 2 and n are as defined above with polyphosphoric acid at a temperature of 110° to 130° C. to produce a 4-oxo-1,2,3,4-tetrahydroquinoline intermediate of the formula ##SPC11## wherein R 1 is hydrogen, and R 2 and n are as defined above; (2) reacting the product of step 1 with a dialkyl alkoxymethylene malonate at a temperature of 130° to 200°C. to effect condensation of the reactants to form an N-substituted tetrahydroquinoline intermediate of the formula ##SPC12## wherein R 1 R 2 , n and alk are as defined above; (3) condensing the produce of step 2 at a temperature of 100 to 140°C. in the presence of polyphosphoric acid to form an alkyl 1,7-dioxo-benzo [ij]quinolizine-2-caboxylate intermediate of the formula ##SPC13## wherein R 1 , R 2 , n and alk are as defined above; and (4) saponifying the product of step 3 to form a 1,7-dioxo-benzo[ij]quinolizine-2-carboxylic acid intermediate of the formula ##SPC14## wherein R 1 , R 2 , and alk are as defined above; (5) reducing the product of step 4 with a selective metal hydride to form the final product.