GB1266587A - - Google Patents

Abstract

1,266,587. Azetidinol derivatives. SCHERICO Ltd. 27 June, 1969 [28 June, 1968], No. 32669/69. Heading C2C. Novel compounds I in which R 1 is OH or hydroxy etherified or esterified by a pharmaceutically acceptable moiety; R 2 is aryl optionally substituted by OH, alkyl, cycloalkyl, alkoxy, halo or haloalkyl; R 3 and R 4 are H, alkyl, cycloalkyl or aryl; and R 5 is alkyl, cycloalkyl, alkenyl, cycloalkenyl or aralkyl, all of which may be substituted by OH, alkoxy, acyloxy or halo and their salts are prepared (1) by reaction of compounds II with R 7 -R 5 (R 6 and R, are reactive groups); (2) by condensation of compounds IV with oxo compounds R 8 -CO-R 9 followed by reduction of the condensate to give I where R 5 is CHR 8 R 9 ; (3) reducing a double bond in starting compounds differing from compounds I in that they contain one or more non-aromatic double bonds; and (4) subjecting compounds R 5 -NR 14 (R 15 ) (R 11 is H or and R 16 is an acid radical which is eliminated; R 15 is H or R 18 C00R 19 ; R 18 is alkylidene, R 19 is alkyl) either when R 14 is H to condensation with R 17 CH(R 3 )-CR 1 R 2 -CH(R 4 )-R 17 (R 17 is a radical derived from an acid, which radical is eliminated during reaction) or when R 14 is -CHR 3 -CR 1 R 2 -CHR 4 R 16 to intramolecular condensation. Intermediates isolated are those prepared in the following sequence: 3-azetidinol is reacted with benzoyl chloride to give 1-benzoyl-3- benzoyloxyazetidine; which is then reacted with KOH to give 1-benzoyl-3-azetidinol; which is then oxidized to 1-benzoyl-azetidin-3-one; which is then reacted with C 6 H 5 MgBr to give 1 - benzoyl - 3 - phenyl - 3 - azetidinol; which is then refluxed with NaOH to give 3-phenyl-3- azetidinol (which may also be prepared by catalytic hydrogenation of 1-(α-phenethyl)-3-phenyl-3-azetidinol); which is then acetylated to give 1 - acetyl - 3 - acetoxy - 3 - phenyl - azetidiec. 1 -Benzcyl-3-phenyl-3-azetidinol is prepared by U.V. irradiation of N-methyl-α-benzamidoacetophenone. Pharmaceutical compositions comprise a compound I together with a suitable excipient for oral or parenteral administration as analgesics.