Piperidine, acetate

Aminobutenones of Z-configuration having at least one hydrogen atom attached to the amino group (80MI1) condense with aldehydes (EtOH, piperidine acetate, 25°C, 12 h) in 2 1 ratio to form 1,4-dihydropyiidine derivatives 290 (50NKZ1061). 

The synthesis of 2,3-dihydro-5-oxaisothiazole[5,4-i]pyridme 321 was performed from monothiomalonamide (319) and methoxybutenone (85S861). 2-Thioxo-l,2-dihydropyridine-3-carboxamide 320 forming in the first stage (piperidine-acetate, EtOH, 10 h, yield 87 %) was further oxidized to isothiazolopy-ridine 321, yield 95%. 

A 3-1., three-necked flask fitted with a mechanical stirrer, a dropping funnel, and a thermometer is then charged with an aqueous solution of 2.2 moles of calcium hypochlorite [Hypochlorous acid, calcium salt] (Note 3), and the piperidine acetate prepared above is placed in the dropping funnel. The hypochlorite solution is stirred and cooled to 0° to — 5° with a methanol-ice bath, and the piperidine acetate is added dropwise over a period of 1.25 hours while the temperature is maintained below 0°. After a further 15 minutes of stirring, equal portions of the mixture are placed in two 2-1. separatory funnels and extracted three times with a total of about 1300 ml. of ether. The ether extract is placed in a 2-1. flask and dried over anhydrous sodium sulfate in a cold room at 4° overnight. After filtration to remove inorganic material, the bulk of the ether is removed by boiling on a water bath maintained below 60° (Note 4). 

Carboxy-3,5-dichlorophenyl diazo-nium chloride, 31, 97 Catalyst, ammonium acetate, 31, 25, 27 copper chromite, 31, 32 ferric nitrate, hydrated, 31, 53 piperidine, 31, 35 piperidine acetate, 31, 57 Catechol, 33, 74... 

Piperidine acetate, 32, 33 Potassium, 30, 19, 20 directions for safe handling of, 30, 20 Potassium acid acetylenedicarboxylate, 32, 55... 

A novel synthesis of alkylsulfanylisothiazoles 230 starts with sodium a-cyanoketene dithiolates 227, obtained by the reaction of cyanoacetamides 226 with carbon disulfide in the presence of sodium ethoxide <06SC825>. Treatment of 227 with sulphur and piperidine acetate generates sodium isothiazole-3,5-dithiolates 229. The formation of 229 is assumed to arise from the addition of anionic sulphur to the nitrile group in 227 to give the intermediate 228, which cyclizes upon elimination of anionic sulphur to yield 229. Salts 229 are readily alkylated to furnish 3,5-bis(alkylthio)isothiazole derivatives 230. 

Metabolism - Dexmethylphenidate is metabolized primarily to c/- -phenyl-piperidine acetic acid (also known as c/-ritalinic acid) by de-esterification. This metabolite has little or no pharmacological activity. 

Mefabo//sm - Methylphenidate is metabolized rapidly primarily via deesterification to alpha-phenyl-piperidine acetic acid (PPA or ritalinic acid). The metabolite has little or no pharmacologic activity. 

Note 5) in 400 ml. of water and piperidine acetate (prepared by adding piperidine to 8 ml. of glacial acetic acid in 20 ml. of water until the solution is just basic to litmus). The flask is equipped with a reflux condenser, and the mixture is heated under reflux for 2 hours. At the end of this time 200 ml. of water is added, and the solution is acidified (to litmus) with acetic acid, causing separation of the product as a voluminous yellow precipitate. The mixture is cooled in an ice bath for 2 hours, and the product is collected on a suction filter, washed on the filter with three 100-ml. portions of ice water, and dried (Note 6). The yield of 3-cyano-6-methyl-2(l)-pyridone is 59-67 g. (55-62%) m.p. 292-294° (dec., cor.) (Notes 7, 8, and 9). 

If not all the ether is removed, it will be impossible to obtain the reflux temperature needed for the subsequent condensation, in which case the remainder of the ether must be removed by a preliminary distillation after adding the aqueous solution of cyanoacetamide and piperidine acetate. 

Catalyst, piperidine, 31, 35 piperidine acetate, 81, 57 Raney nickel, 36, 21, 38, 22 sulfuric acid, 34, 26 Catechol, 33, 74 Cetylmalonic acid, 34,16 Cf.tylmalonic ester, 34,13 Chlorination, by sulfuryl chloride, 33, 45, 37,8... 

The benzofuran-3-carbaldehyde (398) is the key intermediate in the synthesis of rus-codibenzofuran. Condensation of (398) with Meldrum s acid in the presence of piperidine acetate afforded the arylmethylene derivative (399), which on flash vacuum pyrolysis gave the benzofuranol (400) (Scheme 107) (80AJC1817). 

The so-called trimerization of propynal in the presence of piperidine acetate provides a synthesis of 4-ethynyI-4//-pyran-3,5-dicarbaldehyde (149) (50LA(568)34> it should be noted that the structure proposed for the product in the original work has been corrected (64CB1959). In the absence of moisture, the reaction fails and it seems likely that the synthesis involves hydration of the alkyne to the divinyl ether. Finally, condensation with the third molecule of the aldehyde results in cyclization to the product (Scheme 20). 

Some supporting evidence for the mechanism is provided by the formation of the 4-ethyl analogue (150) when propynal is treated with piperidine acetate in the presence of propanal the latter may be considered to intercept the divinyl ether. 

EDDA is the best catalyst for the condensation. Piperidine acetate gives side products. 

A solution containing 1.83 g of 3,4-dihydroxy-5-nitrobenzaldehyde, 1.5 g of N,N-diethylcyanoacetamide and catalytic amount of piperidine acetate in 40 ml of dry ethanol was refluxed over night. After cooling the solvent was evaporated in vacuo and the residue was recrystallized from water-dimethylformamide. Yield of desired product was 2.23 g (73%), melting point 153°-156°C. 

Dimethyl sulfate Phosgene Piperidine Acetic acid... 

Catalyst, alumina, 34, 79, 35, 73 ammonium acetate, 31, 25, 27 boron tnfluonde etherate, 38, 26 copper chromite, 31, 32, 36, 12 cupric acetate monohydrate, 38, 14 cuprous oxide silver oxide, 36, 36, 37 ferric nitrate, hydrated, 31, 53 phosphoric acid, 38, 25 piperidine, 31, 35 piperidine acetate, 31, 57 Raney nickel, 36, 21, 38, 22 sulfuric acid, 34, 26 Catechol, 33, 74 Cetylmalonic acid, 34, 16 Cetylmalonic ester, 34,13 Chlorination, by sulfuryl chloride, 33, 45, 37, 8... 

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