Patent GB-1193686-A (GB)
Title: Derivatives of Bis(p-Hydroxyaryl Alkanoic Acids
Inventor: FRIED JOSEF
IPC: C07C37/11
Filed: 1967-04-25
Abstract: 1,193,686. Bis(substituted - phenyl) - compounds. E. R. SQUIBB & SONS Inc. 25 April, 1967, No. 19047/67. Heading C2C. Novel compounds of the Formula I and acid addition salts thereof wherein P represents one of the radicals of the formulµ wherein R represents hydrogen, hydroxy, nitro, lower alkyl, lower alkoxy, lower alkanoyl, halo or dialkylamino-lower alkylene, R<SP>1</SP> represents hydrogen or lower alkyl, R<SP>2</SP> represents hydrogen or hydroxy and R<SP>3</SP> represents hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl, cycloalkyl, aralkyl, cycloalkyl-lower alkyl, thienyl, pyridyl, thienyl-lower alkyl or pyridyl - lower alkyl or R<SP>2</SP> and R<SP>3</SP> together represent oxo, R<SP>4</SP> represents lower alkynyl, aryl, cycloalkyl, aralkyl, cyoloalkyl-lower alkyl, thienyl, pyridyl, thienyl-lower alkyl or pyridyl-lower alkyl, and n is an integer from 1 to 5 (lower means 1 to 8 carbon atoms); (a) the preparation of a compound I (R, R<SP>1</SP> and R<SP>2</SP> have the above significance and R<SP>3</SP> and R<SP>4</SP> are the same or different but do not represent alkyl or alkenyl) by reacting a compound of the formula with a Grignard reagent in excess and then with water to form a compound of formula and, if desired, reacting the latter compound with a fatty acid anhydride to eliminate one mole of water, hydrolysing the latter compound in the core where R<SP>1</SP> represents hydrogen with a base to form a compound of the formula and, if desired, wherein R<SP>1</SP> of the latter compound is hydrogen, reacting the said compound with an alkali metal alkoxide and a halide R<SP>1</SP>-Hal in which R<SP>1</SP> is lower alkyl to form the corresponding compound wherein R<SP>1</SP> represents lower alkyl and, if desired, hydrogenating to form a compound of formula and (b) the preparation of a compound I (R, R<SP>1</SP> and R<SP>2</SP> have the above significance, R<SP>3</SP> is hydrogen, R<SP>4</SP> is lower alkynyl, aryl, cycloalkyl, aralkyl, cycloalkyl-lower alkyl, thienyl, pyridyl, thienyl-lower alkyl or pyridyl-lower alkyl or R<SP>2</SP> and R<SP>3</SP> together represent oxo), by reacting a compound of formula wherein R<SP>6</SP> is lower alkyl or a protecting group, with an R<SP>4</SP>-cadmium reagent to form a compound of formula and removing the protecting group or reducing the compound of the previous formula to form the corresponding compound in which the oxo group is replaced by H(OH) and, if desired, reacting with a fatty acid, hydrolysing, if desired reacting with a halide R<SP>1</SP>-Hal and, if desired, hydrogenating as in reaction (a) Pharmaceutical compositions for oral or parenteral administration contain a compound of Formula I above as the active ingredient. The active compounds are hypocholesteremic agents. 4,4 - Bis[4 - benzyloxyphenyl]valeric acid is prepared by reacting 4,4 - bis[4<SP>1</SP>- hydroxyphenyl]valeric acid and benzyl chloride. The acid may be converted to the corresponding acid chloride. Ethyl 4,4 - bis(3 - methoxy - 4 - hydroxyphenyl)pentanoate is prepared by reacting omethoxyphenol and ethyl levulinate.