3- Piperidinol derivatives, synthesis

A synthesis of an extended l,2,3,4-tetrahydro-j8-carbohne system (73) is somewhat similar. The 4-o-aminophenyl-3-piperidinol derivative 72, obtained in several steps from cinchonine, undergoes... 

Synthesis (Kleemann et al. 1999, Janssen (Janssen), 1973 Janssen et al. (Janssen), 1973, Stokbroekx et al., 1973, Niemegeers et al., 1974) ) Treatment of 2-oxo-3,3-diphenyl-tetrahydrofuran, synthesized by treatment of diphenyl-acetic acid ethyl ester with ethylene oxide, with HBr(gas) yields bromo derivative i, which is then converted into butyryl chloride derivative ii by means of thionyl chloride in refluxing chloroform. Reaction of derivative ii with dimethylamine in toluene affords dimethyl (tetrahydro-3,3-diphenyl-2-furylidene)ammonium bromide, which is then condensed with 4-(4-chlorophenyl)-4-piperidinol by means of Na2C03 and Kl in refluxing 4-methyl-2-pentanone to provide loperamide. 

Finally, the type IV chiral building block 15 was synthesized via the iminium reduction of the corresponding iminiun salt derived from the vinylogous urethane 14 as shown in Scheme 5. With all four stereoisomers of the chiral building blocks (I IV) for synthesis of 3-piperidinol alkaloid in hand, we examined the synthesis of prosafrinine,... 

Variations of the benzomorphan analgesics which have been reported include the bis-desmethyl compound (ll) 5 and compounds v/ith complex nitrogen substituents (l2,K=CIi and 3r H =K, CHj and CgH ), none of which shows marked activity. The 5-phenyl derivatives (13,R=H) are the subject of a patent.25 The levo isomer of the phenvl substituted derivative (l3,2=GIIj) shows morphine level analgesia v/ith no capacity to substitute for morphine in addicted rats on the other hand, the dextro isomer is inactive as an analgesic yet suppresses the abstinence syndrome. A ready synthesis of benzornorphans by cyclization of 2-substituted benzyl-1, 3-diraethyl-4-piperidinols has been patented. 

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