2-Methyl-3-hydroxy-piperidine

Disubstituted piperidines (and piperideines) are well known as constituents of myrmicine ant venoms, particularly in fire ants of the genus Solenopsis (125,134,149,161,164). Both cis and trans isomers occur. Cis-and/or rrans-2-methyl-6-nonylpiperidines are prominent ant alkaloids. These ant alkaloids have not been detected in amphibians, but the 4-hydroxy piperidine analog (241D) has. 

Bu SnF added to a soln. of Sn(OTf)2 and (S)-l-methyl-2-[(piperidin-l-yl)methyl]pyr-rolidine in dichloromethane at room temp., stirred for 30 min, cooled to —78°, S-ethyl ethanethioate trimethylsilyl enol ether in the same solvent added, followed after 30 min by benzaldehyde in dichloromethane, and stirring continued for 12 h before quenching with aq. NaHC03 S-ethyl 3-hydroxy-3-phenylpropanethioate. Y 78% (e.e. 82% 0% in the absence of BujSnF). F.e. and chiral diamines s. S. Kobayashi, T. Mukaiyama, Chem. Letters 1989, 297-300. 

Piperidine, l-(2-hydroxythiobenzoyI)-neutron diffraction, 2, 116 Piperidine, 4-hydroxy-2,2,6-trimethyI-as local anaesthetic, 1, 179 Piperidine, JV-methoxycarbonyl-electrolytic oxidation, 2, 374 Piperidine, 2-methyl-synthesis, 2, 524 Piperidine, 3-methyI-mass spectrometry, 2, 130 Piperidine, C-methyl-NMR, 2, 160 Piperidine, JV-methyl- C chemical shifts, 2, 15 catalyst... 

The solvent was evaporated from the combined benzene extracts to give 33.4 g of a clear light brown resin. Crystallization from an alcohol-water mixture gave 19.5 g of 1-methyl-4-(5-hydroxy-5-dibenzo[a,e] cycloheptatrienyO-piperidine, MP 156° to 157°C. Two recrystallizations from alcohol-water mixtures followed by two recrystallizations from benzene-hexane mixtures gave analytically pure product, MP 166.7° to 167.7°C. 

Cl Preparation of 1 -Methyt-4-(5-Dibenzo[a,e] Cydoheptatrienytidenej-Piperidine Hydrochloride 1-Methyl-4-(5-hydroxy-5-dibenzo[a,e] cycloheptatrienyO-piperidine (3.05 g,... 

A solution of 192 g of 1 -phenethyl-4-hydroxy-4-aminomethyl piperidine in BOO cc of diethyi-carbonate is heated for 1 /i hours to refiux at about B0°C in the presence of sodium methylate (prepared for immediate use from 2 g of sodium). After this time, the ethyl alcohol formed during the reaction is slowly distilled while the maximum temperature is reached. The excess ethyl carbonate is distilled under reduced pressure. A crystallized residue Is then obtained, which is stirred with 400 cc of water and 400 cc of ether. The solution is filtered and 125 g (77.6%) of practically pure product melting at 232°C to 233°C, are obtained. 

The u.v.-visible spectrum of the 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl-methyl-cobinamide is very similar to methyl-cobin-amide itself and as a result this technique cannot be used to rigorously identify the spin labeled derivative. The spin labeled compound does show a spectral change with pH between pH 7.0 and pH 2.0 which methyl-cobinamide does not exhibit. Despite the similarities between methyl-cobinamide and nitroxylmethylcobinamide, the circular dichroism spectrum of the two derivatives are quite different. Fig. 23 shows the marked difference in C. D. spectra of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl, methylcobinamide, and a methylcobinamide solution containing an equimolar amount of uncoordinated nitroxide. 

Fig. 23. C. D. Spectra of 4-hydroxy-2,2,6,6-piperidine-N-oxyl-methyl-cobinamide (—) and methyl-cobinamide plus free nitroxide (---—) at 3 x 10 5 M in ethanol...

Recently, SB-269970 (l-[3-hydroxy-phenyl-sulphonyl]-2-[2-(4-methyl-l-piperidinyl)-ethyl] pyrrolidine) and SB-656104 (6-((R)-2- 2-[4-(4-chloro-phenoxy)-piperidin-l-yl]-ethyl pyrrolidine-l-sulphonyl)-lH-indole) have been reported to be potent 5-HT7 receptor antagonists (Hagan et al., 2000 Forbes et al., 2002). Selective 5-HT7 receptor agonists are not available at the present time. Systemic administration of SB-269970 or SB-656104 to rats at the beginning of the light period has been shown to reduce the total amount of REMS and to increase REMS latency. Values of W and SWS were not significantly modified (Hagan et al., 2000 Thomas et al., 2003). Hedlund et al. (2005) established that 5-HT7... 

Figure 4.4 Stereospecific esterification synthesis of (/t)-/V-(fe/V-hutoxycarbonyl)-3-hydroxyinethyl-piperidine from (7 ,5)-A,-(/< r7-butoxycarhonyl)-3-hydroxy methyl piperidine applying a sequence of stirred-tank reactor, extraction module, second stirred-tank reactor and second extraction module... 

Greenbeger LM, Annable T, Collins KI, Komm BS, Lyttle CR, Miller CP, et al. (2001) A new antiestrogen, 2-(4-hydroxy-phenyl)-3-methyl-l-[4-(2-piperidin-l-yl-ethoxy)-benzyl]-lH-indol-5-ol hydroclorhide (ERA-923), inhibits the growth of tamoxifen-sensitive and -resistant tumors and is devoid of uterotropic effects in mice and rats. Clin Cancer Res 7 3166-3177... 

Dieckmann condensation of piperidine-2-carboxylate 138 in toluene in the presence of NaOEt furnished pyrido[l,2-h]pyridazine-3-carboxylate (139) (71CPB159). Ethyl 2-methyl-4-hydroxy-5,6-dihydro-4a//-pyridaz-ino[l,6-a]quinoline-3-carboxylate (7,8-benzolog of 139) was prepared similarly (66YZ613). 

Very interesting results concerning the cytotoxicity of alkaloids isolated from the flowers of ornamental legume plant Senna spectabilis have been noted by Sriphong et al. . N,0-diacetylcassine, 3(f )-benzoyloxy-2(f )-methyl-6(f )-(lh-oxododecyl)-piperidine and 5-hydroxy-2-methyl-6-(lh-oxododecyl)-pyridine V-oxide exhibited cytotoxicity against KB cell lines. 

Das ziemlich einfach herstellbare 1 -Hydroxy- 1-piperidino-cyclopropan kann in Gegen-wart von Titan(IV)-chlorid in einer Variante der Mannich-Reaktion als Aquivalent von Cyclopropanon/Piperidin dienen nach der anzunehmenden in-situ-Umwandlung in 1-Cyclopropyliden-piperidinium-chlorid erfolgen Reaktionen z.B. mit 1-Trimethylsiloxy-cyclohexen zu 2-Oxo-l-(l-piperidino-cyclopropyl)-cyclohexan (63%) und mit 1-Methyl-pyrrol bzw. Indol zu l-Methyl-2-( 1-piperidino-cyclopropyl)-pyrrol (65%) bzw. 3-(l-Pipe-ridino-cyclopropyl)-indol (84%)2 ... 

---