1-Substituierte-4-Phenoxypiperidine und Verfahren zu ihrer Herstellung

摘要

1280699 Piperidine derivatives A H ROBINS CO Inc 19 Dec 1969 [23 Dec 1968 7 Nov 1969] 61969/69 Heading C2C Novel piperidine derivatives of the Formula I wherein R is CONH 2 , C 1-8 alkylcarbamoyl, di- (C 1-8 alkyl)carbamoyl, unsubstituted or monosubstituted phenylcarbamoyl monosubstituted benzoylalkyl, mono- or disubstituted phenoxyalkyl, CH 3 CH 2 OCO, or HOCH 2 CHOHCH 2 -, R1 is H, C 1-8 alkyl, C 1-8 alkoxy, CF 3 , F, Cl or Br, and R2 is H or CH 3 CO, and the acid addition salts of those compounds posessing a basic nitrogen atom are prepared by reacting the corresponding piperidine compounds unsubstituted in the 1-position with compounds selected from nitrourea, metal cyanates, C 1-8 alkyl isocyanates, N,N-di-(C 1-8 alkyl)-carbamoyl halides, unsubstituted or monosubstituted phenyl isocyanates, monosubstituted benzoylalkyl halides, mono- or di-substituted phenoxyalkyl halides ethyl chloroformate and 3-halo-1,2-dihydroxypropanes. 4 - (2 - Methoxyphenoxy)piperidine is obtained by hydrolysing 1-acetyl-4-(2-methoxyphenoxy)piperidine, obtained by reacting the tosylate ester of 1-acetyl-4-hydroxypiperidine with 2-methoxyphenol. By a similar process 4 - (4 - methoxyphenoxy) -, 4 - 4(p - chlorophenoxy) - and 4 - (4 - acetyl - 2 - methoxy) - piperidine and their corresponding 1-acetyl derivatives are prepared. 4 - (3 - Trifluoromethylphenoxy)piperidine hydrochloride is made by hydrolysing the corresponding 1-acetyl compound and converting the resulting base into the hydrochloride. 1 - Benzyl - 4 - (p - bromophenoxy)piperidine hydrochloride and 1 - benzyl - 4 - phenoxypiperidine hydrochloride are obtained by reacting 1- benzyl-4-piperidinol with p-bromofluorobenzene and fluorobenzene respectively and converting the resulting free bases into the hydrochlorides. 4 - (p - Trifluoromethylphenoxy)piperidine is prepared by the hydrogenolysis of 1-benzyl-4-(ptrifluoromethylphenoxy)piperidine obtained by reacting 1-benzyl-4-piperidinol with p-fluorotrifluorobenzene. Pharmaceutical compositions, suitable for oral or parenteral administration contain the above novel piperidine derivatives or acid addition salts thereof and pharmaceutically acceptable carriers or excipients - The compounds have mucsle relaxant and/or anticonvulsive and/or tranquilizing activities. Reference has been directed by the Comptroller to Specification 1,031,749.