Patent GB-1268831-A (GB)
Title: Tertiary amino acids, process for their manufacture and compositions containing them
IPC: C07D295/027
Filed: 1969-03-26
Abstract: 1,268,831. α(Cyclicaminophenyl) - aliphatic carboxylic acids. CIBA-GEIGY A.G. 26 March, 1969 [27 March, 1968; 3 Sept., 1968; 13 Jan., 1969], No. 15859/69. Heading C2C. Novel compounds of Formula I in which R 1  represents a hydrogen atom or a lower alkyl, cycloalkyl or cycloalkyl-lower alkyl group; Ph represents a phenylene radical or a phenylene radical substituted by one or more of the same or different substituents selected from lower alkyl, free hydroxy, free mercapto, lower alkoxy, lower alkylmercapto, halogeno, trifluoromethyl, nitro and amino groups; and A represents a lower alkylene or lower alkenylene radical that is unsubstituted or substituted by one or more of the same or different substituents selected from lower alkyl, hydroxy, mercapto, lower alkoxy, lower alkanoyloxy, lower alkylmercapto, halogeno and oxo groups; provided that R 1  represents a cycloalkyl or cycloalkyllower alkyl group, and/or A represents a lower alkenylene radical which may be substituted as defined above; and the functional acid and amino derivatives i.e. esters, amides, thioamides, morpholides, nitriles, hydroxamic acids, ammonium and metal salts, N-oxides, lower alkyl or phenyl lower alkyl, quaternary ammonium compounds and acid addition salts, ("lower" above and hereinafter denotes groups or compounds containing up to 7 carbon atoms) are prepared (a) by reacting a compound of Formula II in which A has the meaning given for Formula I and X 1  represents a grouping of the formula -CH(R 1 )-Y 1 , in which Y 1  represents an alkali metal atom, a halogeno-magnesium group or a reactive, esterified or etherified hydroxyl group, with a reactive derivative of carbonic acid or of formic acid, not more than one of the reactants containing a metal atom; or (b) oxidizing in a compound of the Formula II in which X 1  represents a grouping of the formula -CH(R 1 )-Y 2 , in which Y 2  represents a hydroxymethyl or borylmethyl group, a formyl group or a 1-lower alkenyl or lower alkenoyl group, the group represented by Y 2 ; or (c) reacting a compound of the Formula II in which X 1  represents a grouping of the formula -CH(R 1 )-Y 2 , in which Y 2  represents an ammonium group, with a metal cyanide; or (d) decarbonylating a compound of the Formula II in which X 1  represents a grouping of the formula -CH(R 1 )-Y 2 , in which Y 2  represents a carboxycarbonyl group; or (e) reacting a compound of the Formula II in which X 1  represents an acetyl group, with sulphur in the presence of ammonia or a primary or secondary amine; or (f) reacting a compound of the Formula II in which X 1  represents a halogeno-carbonyl group, with an R 1 -diazo compound and rearranging it by hydrolysis, alcoholysis, ammonolysis or aminolysis; or (g) reacting a compound of the Formula II in which X 1  represents a 1-lower alkenyl group, with carbon monoxide and water under acidic conditions; or (h) decarboxylating a compound of the Formula II in which X 1  represents a free or functionally converted grouping of the formula -C(R 0 )(R 1 )-C(=O)-OH, in which R 0  represents a carboxy group; or (j) converting in a compound of the Formula II, in which X 1  represents a free or functionally converted grouping of the formula or of the formula -C(=R 1 <SP>0</SP>)-C(=O)-OH, in which R represents a free or reactive esterified hydroxyl group, and R 1 <SP>0</SP> represents a lower alkylidene or cycloalkylidene group, the group represented by R into a hydrogen atom or the group represented by R 1 <SP>0</SP> into a group represented by R 1 , by reduction; or (k) reacting a compound of the Formula II in which X 1  represents a hydrogen atom or a metal atom or a metal grouping, with a reactive ester of a glycolic acid compound of the formula or a functional acid derivative thereof, in which Y 3  represents a reactive, esterified hydroxyl group; or (m) reacting a compound of the formula or a functional acid derivative thereof, in which X 2  represents a reactive esterified hydroxyl group, with a secondary amine of the formula AN-H or an alkali metal derivative thereof, or (n) reacting a compound of the Formula III in which X 2  represents a primary amino group, with a reactive esterified glycol of the formula HO-A-OH; and, if desired, converting an acid or amine group into the required derivative or a resulting derivative into the free acid and, if desired, reacting a compound of Formula I where R 1  is H with a metal and then a reactive ester of an alcohol R 1 OH, and if desired, followed by salt formation and/or resolution. α-Cyclopropyl-α-(4-piperidinophenyl) acetaldehyde is prepared by action of p-toluenesulphonic acid on 1-cyclopropyl-1-(4-piperidinophenyl)-ethylene oxide which is obtained from 4-piperidinophenyl cyclopropyl ketone by action of a reagent prepared from sodium hydride and trimethyl sulphonium iodide in dimethylsulphoxide. Pharmaceutical compositions having antiinflammatory activity and in conventional forms for enteral or parenteral administration comprise an above novel compound and a carrier therefor.