Patent GB-1291386-A (GB)
Title: Improvements in or relating to 2-(6'-substituted-2'-naphthyl) propionic acid derivatives and salts thereof
IPC: B01D9/02
Filed: 1970-01-20
Abstract: 1291386 Salts and resolved optical isomers of 2 - (6<SP>1</SP> - substituted - 2<SP>1</SP>- naphthyl) propionic acids SYNTEX CORP 20 Jan 1970 [24 March 1969] 2764/70 Addition to 1211134 Heading C2C Novel compounds of the Formula I wherein one of R<SP>1</SP> and R<SP>2</SP> is hydrogen and the other is methyl or difluoromethyl; R<SP>3</SP> is methyl, ethyl, isopropyl, cyclopropyl, trifluoromethyl, vinyl, ethynyl, fluoro, chloro, methoxy, methoxymethyloxy, difluoromethoxy, methyl thio, methoxymethyl thio or difluoromethyl thio, either in the form of a mixture of d- and lisomers or resolved isomers of the salts with magnesium, ammonium, R 3 N, ethanolamine, methyl glucamine or ethylenediamine, where R is C 1-6  alkyl except ethyl, monocyclic aralkyl or monocyclic aryl or in the form of the resolved d- and l-forms of the free acid or additionally the sodium, potassium, calcium, aluminium, 2-(diethylamino)ethanol, 2 - (dimethylamino)- ethanol, argurine, lysine, caffeine, procaine and triethylamine salts with the proviso in the latter case that when the compound is in the form of the free acid and the other of R<SP>1</SP> and R<SP>2</SP> is methyl, R<SP>3</SP> is cyclopropyl, vinyl, ethynyl, methoxymethyloxy or methoxylmethyl thio may be prepared by either or both of the steps (a) resolving a compound of the Formula I to obtain a d- or l-isomer and (b) reacting a compound I with a base to form the corresponding salt; and optionally one or more of the following steps; (c) hydrolysis of an ester of a compound I, (d) decarboxylation of a 2-(6<SP>1</SP>-substituted-2<SP>1</SP>- naphthyl) - 2 difluoromethyl malonic acid, (e) etherification of compound I in which R<SP>3</SP> is hydroxy or thiol or (f) dehydrobrominating a 2 - [6<SP>1</SP> - (1,2 - dibromoethyl) - 2<SP>1</SP> - naphthyl propionic acid to yield a 2-(6<SP>1</SP>-ethylnyl-2<SP>1</SP>-naphthyl) propionic acid, (g) fluorinating a compound I in which R<SP>3</SP> is CH 3 S or CH 3 O to R<SP>3</SP>=CF 2 HS or CF 2 HO; (h) fluorinating I in which R<SP>3</SP> is CH 3 - to CF 3  via the trichloro compound, (i) oxidizing I in which R<SP>3</SP> is CH 3 CHOH to CH 3 CO; (j) #- methylating a naphthalene acetic ester. The intermediate 2-(6<SP>1</SP>-methoxy-2<SP>1</SP>-naphthyl) acetic acid may be prepared by Friedel-Crafts acetylation of 2-methoxynaphthalene to form 2 - acetyl - 6 - methoxy naphthalene which is converted by a Willgerodt reaction to the required intermediate. The intermediate diethyl 2-(6<SP>1</SP>-methoxy-2<SP>1</SP>- naphthyl) - 2 - difluoromethylmalonate may be - prepared from 2 - (6<SP>1</SP> - methoxy - 2<SP>1</SP>- naphthyl) acetic acid by esterification followed by treatment with diethyl carbonate in strong base. The intermediate 2 - [61 - (1,2 - dibromoethyl)- 2<SP>1</SP>-naphthyl propionic acid may be formed by brominating 2 - (6<SP>1</SP>- vinyl - 2<SP>1</SP> - naphthyl) - propionic acid. Pharmaceutical compositions of the compounds I show anti-inflammatory and antipyretic activity when administered orally or parenterally with the usual excipients.