Patent GB-1398072-A (GB)
Title: Cyclopentane derivatives
IPC: C07C45/30
Filed: 1972-01-25
Abstract: 1398072 Cyclopentanones MAY & BAKER Ltd 13 June 1972 [14 June 1971 25 Jan 1972] 27844/71 and 3455/72 Headings C2C and C2P The invention comprises a process for preparing cyclopentanones of the Formula I wherein R 1  is C 1-10  alkyl, which may be substituted by an alkoxy group, C 5-7  cycloalkyl or adamantyl; R 2  is H, alkyl or carboxylic acyl; R 3  is carboxy, C 2-13  alkoxycarbonyl, or a carbamoyl or carbazoyl group which is optionally substituted by 1 or 2 alkyl groups; R 4  is an oxygen atom, hydroxyimino, or alkoxyimino, or a hydrazono group which is optionally substituted by 1 or 2 alkyl groups; R 5  is H or alkyl; X is trans-vinylene or ethylene; and n is 5, 6, 7 or 8; and non-toxic salts thereof, the compounds being novel provided at least one of the symbols R 1 , R 2 , R 3 , R 4 , R 5  and n has a significance as specified below:- R 1  is CH 3 , C 8-9  alkyl, a branched chain C 3-7  alkyl, alkoxyalkyl, cycloalkyl or adamantyl; R 2  is alkyl; R 3  is optionally substituted carbamoyl or carbazoyl, or C 12-13  alkoxycarbonyl; R 4  is hydroximino, alkoxyimino or optionally substituted hydrazono R 5  is alkyl; n is 5, 7 or 8; and the novel compound 2#-(3#-hydroxyocttrans - 1 - enyl) - 5 - oxocyclopentaneheptanoic acid and the non-toxic salts of the above novel acids. The said processes comprise (i) reacting enamines of the appropriate 2-R 5 -cyclopentanones with aldehydes of the general formula R 6 O(CH 2 ) n CHO wherein R 6  is H or an acid libile group, followed by acidic hydrolysis and then heating the product with acids to form the corresponding 4-R 5 -2-hydroxyalkylcyclopent-2- en-1-ones, (ii) reacting the above cyclopentanones with a source of HCN to form 4-R 5 -2- hydroxy - alkyl - 3 - oxocyclopentanecarbonitriles, (iii) converting by known methods the above nitriles into ketals or oximes of the formula wherein A is >C(OR 7 ) 2  or >C=NOR 8 , wherein the symbols R 7  are identical alkyl radicals or together form an optionally substituted ethylene radical and R 8  is alkyl; (iv) reducing the ketals or oximes to convert the cyano group to a formyl group; (v) reacting the 2-(hydroxyalkyl)cyclopentanecarbaldehydes with phosphoranes of the formula Q 3 P=CH-CO-R 1 , wherein Q is phenyl optionally substituted by alkyl or alcyl, to form ketones of the Formula VII (vi) oxidizing the ketones of Formula VII above to form the corresponding cyclopentanealkanoic acids, (vii) reducing the oxo group in the above acids to form 2-(hydroxyalkenyl) cyclopentanealkanoic acids of the Formula IX and (viii) converting the ketal group or, if desired, oxime group in the compounds of Formula IX above to an oxo group, and, if desired, converting the resulting compounds into other compounds of the Formula I above or into non-toxic salts thereof. 1 - Chloro - 3 - methylheptan - 2 - one is obtained by reacting 2-methylhexanoyl chloride with diazomethane in the presence of hydrogen chloride. Phosphoranes of the formula are obtained by reacting an aqueous solution of sodium carbonate with phosphonium salts of the formula (Ph) 3 P<SP>(+)</SP>-CH 2 -CO.R 1 Cl<SP>(-)</SP> resulting from the reaction between triphenyl phosphine and compounds of the formula ClCH 2 COR 1 . Pharmaceutical compositions, suitable for oral, parenteral, rectal or vaginal administration, contain the above novel cyclopentanones or non-toxic salts thereof in association with pharmaceutical carriers or coatings. The compounds possess pharmacological properties including the production of hypotension, bronchodilation, inhibition of gastric acid secretion and stimulation of uterine contraction.