Phenyl-piperidinol

CN l-[4,4-bis(4-fluorophenyl)butyl]-4-[4-chloro-3-(trifluoromethyl)phenyl]-4-piperidinol... 

The solution of phenyl-lithium is cooled to -20°C and to this a solution of 12.7 grams of l,3-dimethyl-4-piperidone, prepared according to the method of Howton, J. Org. Chem. 10, 277 (1945), in ether is added dropwise with stirring. After the addition, the stirring is continued for a further 2 hours at -20°C. The lithium complex, l,3-dimethyl-4-phenyl-4-oxylithium piperidine, which forms is soluble in the ether and can be recovered there from. To prepare the piperidinol, the lithium complex, while in the reaction mixture is decomposed by the addition of an ice and hydrochloric acid mixture. The acidified layer is separated, basified and extracted with ether. After drying the ether solution and removing the solvent, the residue on distillation in vacuum distills chiefly at 155°C/10 mm, yielding the product, l,3-dimethyl-4-phenyl-4-hydroxypiperidine, which, on crystallization from n-hexane melts at 102°C. On treatment with propionic anhydride catalyzed with a trace of sulfuric acid,... 

RN 77-20-3 MF C16H23NOj MW 261.37 EINECS 201-011-5 CN cis-1,3-dimethyl-4-phenyl-4-piperidinol propanoate (ester)... 

Treatment of l-methyl-4-phenyl-3,4-epoxypiperidine with phenyl-magnesium bromide in refluxing anisole affords a mixture of 1-methyl-4,4-diphenyl-3-piperidinol (27) and l-methyl-4-phenyI-5-hydroxy-3-piperideine (28).21... 

Addition of hypobromous acid to l-methyl-4-phenyl-3-piperideine hydrobromide (127) was accomplished by the action of bromine in aqueous sodium bromide. Treatment of the resulting l-methyl-3-bromo-4-phenyl-4-piperidinol hydrobromide (128) with 10% aqueous sodium hydroxide gave l-methyl-4-phenyl-3,4-epoxypiperidine (129).114 (Compound 128 was formerly given the erroneous structure of l-methyl-5-bromo-4-phenyl-3-piperideine hydrobromide.7)... 

Hydroboration of l-methyl-3-piperideine with (— )-diisopino-camphenylborane (followed by oxidation) gave ( — )-S- 1-methyl-3-piperidinol (132).116 A similar hydroboration of l-methyl-4-phenyl-3-... 

Complete removal of the 4-phenyl substituent of the reversed ester of pethidine results in a drastic fall in potency as judged from tests in mice (see 23, R = Et). However, certain esters of l-methyl-4-piperidinol formed from aromatic acids display antinociceptive activities in the morphine to codeine range of potency (23).<68) A QSAR study of such esters has been made and a substitution pattern of the phenyl group defined for optimal activity/69 The relevance of these compounds to morphine-type analgesics is doubtful since the more active members show marginal or no affinity for opioid receptors of rat brain homogenates and display no physical dependence in monkeys. 

From the viewpoint of preferred conformation a stereochemical correlation between the more potent antipodal forms of /3-prodine and the a-2,5-dimethyl derivative (a-promedol) is not immediately apparent. In the latter compound the dextro isomer, depicted in its axial 4-phenyl chair form (preferred for a-4-piperidinol base, X-ray evidence)/38 is about 20 times more active than the desmethyl parent while the levo form is inactive (see 22).chair form of (+)-a-promedol (23) clearly reveals a stereochemical kinship with (+)-/3-prodine in respect to C-3(5) geometry, and furthermore points to the activity-raising role of axial methyl adjacent to nitrogen when... 

There are no special synthetic features to the conversion of 4-piperidones to corresponding reversed esters (phenyl lithium is generally preferred to a phenyl Grignard as the organometallic reagent, while dehydration products are sometimes encountered when the 4-piperidinols are esterified), but a... 

A sequence in which a metho salt of (+)-a-prodinol is converted to a phenyl ketone of known configuration is shown (Scheme 7.4)(44) (+)-y-prom-edol is likewise degraded to the same levo ketone hence, the two dextro 4-piperidinols have identical C-3(5) configurations/49 The chirality of the antipodal 3-allylprodines is determined by their conversion to corresponding prodlnols, now of established configuration (Scheme 7.5).<48)... 

Finally, the absolute configuration of (-)-/3-2-methyl-4-phenyl-4-piperidinol has been established by X-ray analysis of the hydrochloride (the salt provides the heavy atom necessary to the anomalous dispersion tech-nique).(17) This physical procedure is the method of choice because it avoids problems of racemization and inversion inherent in all chemical transformations however well conceived. 

Methyl-2-oxo-6-phenyl l-(2,2,6,6-telramelhyi-piperidinol)- 1319 C II NOjSj Pyridine... 

Chemical Name cis-1 dlmethy -4-phenyl-4-piperidinol propanoate hydrochloride Common Name -... 

A mixture of 23 parts of the ethyl ester of 4-phenylisonipecotic acid and 15 parts of 2,2-diphenyl-4-bromobutyronitrile in 19 parts of xylene Is heated for 24 hours at 100°-120°C and then cooled and filtered to remove the precipitate of the hydrobromide of the ethyl ester of 4-phenylisonipecotic acid. The filtrate is then extracted with dilute hydrochloric acid and the extract is rendered alkaline by addition of concentrated aqueous potassium hydroxide and extracted with ether. This ether extract is treated with gaseous hydrogen chloride. The resulting precipitate is collected on a filter. The hydrochloride of the ethyl ester of 2,2-diphenyl-4-(4 -carboxy-4 -phenyl-1 -piperidinol butyronitrile thus obtained melts at about 220.5-222°C. See Meperidine hydrochloride for synthesis of 4-phenyl-isonipecotic acid ethyl ester. 

Diethoxymethylsilylpropoxy)-2,2,6,6-tetramethyl] piperidine Methyl salicylate p-Nonyl phenol 1,2,2,6,6-Pentamethyl-4-piperidinol Phenyl phosphonic acid... 

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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