Piperidine, 1-ethyl

Materials Required Benzylpenicillin sodium (say) 0.12 g amyl acetate (previously saturated with 1-ethylpiperidinium benzylpencillin at room temperature, cooled in ice and filtered) 5.0 ml phosphoric acid (20% v/v) 0.5 ml anhydrous sodium sulphate (freshly ignited and powdered) 0.5 g dry acetone (previously saturated with 1-ethylpiperidinium benzylpenicillin at room temperature cooled in ice and filtered) 3.0 ml 1-ethylpiperidine amyl acetate solution (prepared from 1-ethyl piperidine, 1. 0 ml, and amyl acetate, 8.0 ml, saturated at room temperature with 1-ethylpiperidinium benzylpenicillin, cooled in ice and filtered) 1.5 ml dry acetone in amyl acetate (1 1) previously saturated with 1-ethylpiperidinium benzylpenicillin 2.0 ml solvent ether 4.0 ml. 

Theory Benzylpenicillin (sodium or potassium salt) may be assayed gravimetrically by quantitative conversion to the 1-ethylpiperidinium benzylpenicillin derivative. The ultimate precipitation is caused by 1-ethyl piperidine after the respective sodium or potassium salt of benzylpencillin has been duly converted with phosphoric acid to the corresponding penicillanic acid (i.e. parent acid) and the latter finally extracted with amyl alcohol. The reactions may be expressed as follows ... 

The Lukes reduction of l-(ethoxycarbonylmethyl)pyridinium bromide (86, R = H) and l-(l-ethoxycarbonylethyl)pyridinium bromide (86, R = Me) was accompanied by decarboxylation mixtures of the appropriate 1-methyl- or 1-ethyl-piperidine and 3-piperideine were obtained.92... 

Much interesting work has been done in the last ten years on the bridging of pyrrole and piperidine rings. Early in their work on this subject Clemo and Metcalfe (1937) prepared quinuclidine (V) by the reduction of 3-ketoquinuclidine (IV), the latter resulting from the hydrolysis and decarboxylation of the product (III) of a Dieckmann internal alkylation, applied to ethyl piperidine-l-acetate-4-carboxylate (II), itself made by condensing ethyl piperidine-4-carboxylate (I) with ethyl chloroacetate. 

Substituted perhydropyrido[l,2-c][l,3]oxazines 83 were obtained by the cyclization of l-(/er/-butoxycarbonyl)-2-(2-hydroxyalkyl)piperidines 104 in pyridine on the action of MeS02Cl at room temperature (96CJC2434). Cyclization of c/5-2,6-H- l-(methoxycarbonyl)-2-(2-acetoxyhexyl)-9-methox-ypiperidines 105 and 106 in THF in the presence of KO/-Bu yielded 3-butyl-9-methoxyperhydropyrido[l,2-6 ][l,3]oxazin-l-ones 94. Treatment of l-(/erc-butoxycarbonyl)-2-[2-hydroxy-2,2-di(2-propyl)ethyl]piperidine with NaH in boiling THF yielded 3,3-di(2-propyl)perhydropyrido[l,2-c][l,3] oxazin-l-one (01JA315). 

Chemical Name 1 -[ 1 -Mathvl-2-[2-(phenvlmethyl)phenoxv] ethyl] piperidine Common Name —... 

If the more activated alkene 2-vinylpyridine is used in place of styrene with the same catalysts and the same range of substrates, anti-Markovnikoff hydroamination is also found. Thus, N-[2-(2 -pyridyl)ethyl]piperidine was isolated in 53% yield from reaction of 2-vinylpyridine with piperidine in the presence of [Rh(COD)2]+/2PPh3 under reflux. N H addition was observed with other amines, the remaining product in all cases being primarily that from oxidative amination (Table 12). When the catalytic reaction was run in the absence of phosphine, the yield of hydroamination product increased dramatically.171... 

Utilizing Wenkert s cyclization process, a number of new approaches have been elaborated for the synthesis of simple indolo[2,3-a]quinolizine derivatives. For example, treatment of JV-[2-(indol-3-yl)ethyl]piperidine (V-oxide (134) with trifluoroacetic anhydride gave piperideinium intermediate 135 in a Polonovski-type reaction, which could be cyclized in acidic medium to ( )-l (101). 

Oxidative cyclization of N- [2-indol-3-yl)ethyl] piperidine (146) with 3 molar equivalents of mercuric acetate and EDTA disodium resulted in ( )-l in 85% yield (106). 

A 4 g 3-indoleacetic acid (I) in ether. I reat with PCi5 as described elsewhere here to get 2.7 g of the chloride (II). Dissolve 2.7 g (II) in 40 ml ethyl acetate and add 2 ml piperidine (or equimolar amount other amine), 3.5 ml N-ethyl-piperidine in 40 ml ethyl acetate. Let stand three hours at room temperature and filter. Wash filtrate with IN HCI, 10% Na carbonate and evaporate in vacuum to get 1 g of the amide (III) (test for activity). Add 1 g (111) in 25 ml ether to 1.4 g lithium aluminum hydride in 50 ml ether stir four hours at room temperature and reflux one-half hour. Cool and carefully add water until no more bubbling. Add 3 ml 20% NaOH and dry. evaporate in vacuum to get 1 g piperidine analog of DMT... 

F I Cl-CH2-CH-C6H5 (ttberschuss Pipcridin) 90" 1 - (2-Fluor-2-phenyl-ethyl)-piperidin 79 3... 

Auch die Alkalimetalle selbst konnen als Katalysator eingesetzt werden8,9 (s.a. oben Herstellung von l-Ethyl-piperidin) sie bilden mit dem Amin das katalytisch wirksame Alkalimetall-amid. So hat sich fur die Addition von Diethylamin an 4-Ethenyl-4-methyl-benzol zu l-(2-Diethylamino-ethyl)-4-methyl-benzol die Verwendung von Lithium (14mol%) als geeignet erwiesen8. 

Phenyl-trifluormethyl-keton kann in dcr folgenden Weise mit Pipcridin reduktiv zu 1-(1-Phenyl-2,2,2-trifluor-ethyl)-piperidin (60%) aminiert werden3. 

In 1996, a group from Sandoz (now part of Novartis) reported their synthesis of fexofenadine (3). Cbz protection of commercially available ethyl piperidine-4-carboxylate (34) was achieved using Af-(benzyloxycarbonyloxy)succinimide to afford 35. Treatment of 35 with three equivalents phenyl magnesium bromide led to tertiary alcohol... 

N-[4-(Methoxymethyl)-1-[2-(2-thienyl)ethyl]-4-piperidinyl]-/V-phenylpropanamide, N-[4-Methoxymethyl-1 -(2-thiophen-2-yl-ethyl)-piperidin-4-yl]-A/-phenyl-propionamide, C22H30N2O3S, Mr 386.56, mp 96.6 °C citrate (1 1) [60561-17-3], C22H30N2O3S. CgHgOy, Mr 578.68... 

Another total synthesis of sufentanil has been described the cyclization of 2-(2-thienyl)ethylamine with allyl-trimethylsilane and formaldehyde gives 4-hydroxy-1-[2-(2-thienyl)ethyl]piperidine, which is oxidized with oxalyl chloride in DMSO/dichloromethane to 1-[2-(2-thienyl) ethyl]piperidin-4-one. The epoxidation of this compound by means of trimethylsulfonium iodide and the sodium salt of DMSO yields the spiro-epoxide, which is opened with... 

The similar transformations of 1 -benzyl - 4-hydroxy-4- (/1-hydro xy-ethyl)piperidine (24) to 4-bromo- (7) and 4-hydroxyquinuclidines (20)88 are given in the following scheme ... 

Chemical Name l-[l-Methyl-2-[2-(phenylmethyl)phenoxy]ethyl]piperidine Common Name -Structural Formula ... 

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