process for the preparation of pharmaceutical preparations which contain a benzofuranderivaat,and thus formed preparations and process for preparation of pharmacologically active benzofuranderivaten.

摘要

1,266,456. Benzofuran derivatives. RHONEPOULENC S.A. 19 May, 1970 [19 May, 1969], No. 24265/70. Heading C2C. Novel compounds I: wherein R is H or 1-4 C alkyl optionally carrying one halogen atom are prepared by cyclization of compounds II: Intermediates isolated are those prepared in the following sequences: (1) 2-methoxy-3- methylbenzophone is reacted with bromine under ultra-violet light to give 3-bromomethyl-2- methoxy-benzophenone, which is reacted with NaCN to give 3-cyanomethyl-2-methoxy-benzophenone which is then reacted with (a) conc- H 2 50 4 , (b) 48% HBr to give 3-benzoyl-2- hydroxyphenyl-acetic acid; (2) 2-hydroxy-diphenylmethane is reacted with NaH and ethyl -chloroacetylacetate to give ethyl -(2-benzylphenovy) acetyl acetate, which is then reacted with polyphosphoric acid to give 2-ethoxycarbonyl - 3 - methyl - 7 - benzyl - benzofuran; the latter is hydrolysed to 2-carboxy-3-methyl-7- benzyl-benzofuran, which is then reacted with SOCl 2 to give 2-chlorocarbonyl-3-methyl-7-benzylbenzofuran, which on treatment with sodium azide gives 2 -azidocarbonyl-3-methyl-7-benzylbenzofuran; the latter is then reacted. with ethanol under reflux to give 2-ethoxycarbonylamino - 3 - methyl - 7 - benzyl - benzofuran, which on hydrolysis gives 2-oxo-3-methyl-7-benzyl- 2,3-dihydrobenzofuran; the latter is then reacted with NaOH and (CH 3 ) 2 S0 4 to give 2-(3-benzyl-2- methoxyphenyl) propionic acid, which is oxidized to 2 - (3 benzoyl - 2 - methoxy - phenyl) propionic acid using KMnO 4 ; and the methoxy derivative is then reacted with aqueous HBr to give 2 - (3 - benzoyl - 2 - hydroxy - phenyl) propionic acid. Pharmaceutical compositions for oral, rectal, parenteral or topical administration as antiinflammatory agents comprise a compound I together with a suitable diluent or carrier.