2-(4-(2-FLUOROPHENOXY)PHENYL)PROPANOL,PROPIONIC ACID AND ESTERS AND AMIDE THEREOF

摘要

1307284 2 - Phenylpropionic acid derivatives BOOTS CO Ltd 19 April 1971 [16 March 1970] 12570/70 Heading C2C The invention comprises novel 2-phenylpropionic acids of the formula wherein X is O or NH; R 1 is halogen; R 2 and R 3 are H or halogen, at least one of them being H; Y is COOH, CONH 2 or CH 2 OH; together with pharmaceutically acceptable esters, and salts with inorganic and organic bases of those compounds in which Y is COOH, and their preparation. The free acids of the above formula are prepared by the decarboxylation of the corresponding 2 - [3 - R3 - 4 - (4 - R 1 - 2 - R 2 - phenoxy)phenyl] - 2 - methyl - malonic acids or 2 - [3 - R 3 - 4 - (4 - R 1 - 2 - R 2 - anilino)phenyl]- 2-methylmalonic acids. Acids in which X is O may also be obtained by the Ullmann reaction between either 4 - R 1 - 2 - R2 - phenols and 2- (3 - R 3 - 4 - halophenyl) - propionic acids or 4 - R 1 - 2 - R 2 - halobenzenes and 2 - (3 - R 1 - 4- hydroxyphenyl)propionic acids. Acids in which X is NH may be made by hydrolysing compounds of the formula wherein R 5 is an acyl group. The acids thus obtained may be reduced to the corresponding compounds in which Y is CH 2 OH or converted to esters, amides or salts. Other methods of preparation are described in general terms. The following intermediates and starting materials are also prepared: diethyl 2-[4-(4- fluorophenoxy)phenyl]- 2 - methyl - malonate, 4SP1 /SP- (4 - fluorophenoxy)acetophenone, 4 - (4- fluorophenoxy)phenylacetic acid and its ethyl ester, 2 - [4 - (4 - fluorophenoxy)phenyl]- 2- methylmalonic acid, diethyl 2 - [4 - (4 - chlorophenoxy)phenyl] - 2 - methylmalonate, ethyl 4 - (4 - chlorophenoxy)phenylacetate, 41 - (4 fluorophenoxy) - 3SP1/SP- nitroacetophenone, 31- amino - 4SP1/SP - (4 - fluorophenoxy)acetophenone, 3SP1/SP - chloro - 4SP1/SP - (4 - fluorophenoxy)acetophenone, ethyl 3 - chloro - 4 - (4 - fluorophenoxy)phenylacetate, diethyl 3 - chloro - 4 - (4 - fluorophenoxyl)phenyl - 2 - methylmalonate, 4SP1/SP- bromo - 31 - nitroacetophenone, and 2 - [4- (2,4 - difluorophenoxy)- phenyl]propionyl chloride. Pharmaceutical compositions suitable for oral, topical, parenteral and rectal administration, contain the above novel compounds in association with pharmaceutical excipients. The compounds possess anti-inflammatory, analgesic and antipyretic properties.