Pipecolinal

CjHiiNOj 3105-95-1) see Ropivacaine hydrochloride pipecolinic acid 2,6-xylidide... 

C(,Hi2N20 39546-32-2) see Metopimazine Pipamazine piperidine-2-carboxylic acid (2,6-dimetbylanilide) see under pipecolinic acid 2,6-xylidide... 

The utility of lOOC reactions in the synthesis of fused rings containing a bridgehead N atom such as pyrrolizidines, indolizidines, and quinolizidines which occur widely in a number of alkaloids has been demonstrated [64]. Substrates 242 a-d, that possess properly positioned aldoxime and alkene functions, were prepared from proline or pipecolinic acid 240 (Eq. 27). Esterification of 240 and introduction of unsaturation on N by AT-alkylation produced 241 which was followed by conversion of the carbethoxy function to an aldoxime 242. lOOC reaction of 242 led to stereoselective formation of various tricyclic systems 243. This versatile method thus allows attachment of various unsaturated side chains that can serve for generation of functionalized five- or six-membered (possibly even larger) rings. 

The key feature of the first total synthesis of (+)-homopumiliotoxin 223G 418 was a Lewis acid-induced, chelation-controlled propargylation of the trifluoroacetate salt of (. )-2-acetyl pi peri dine 415, derived from iV-Cbz-L-pipecolinic acid. Alkyne 416 thus formed was transformed after several steps into 417, which was cyclized by activation of the primary hydroxyl with the carbon tetrabromide-triphenylphosphine system to give the natural product (Scheme 98) <1998TL2149>. 

Cyclization of 1-carboxypentyl pipecolinate with bis(2-oxo-3-oxazolidinyl)phosphinic chloride in DMF in the presence of Htinig s base afforded 3-butylperhydropyrido[2,l-f][l,4]oxazine-l,4-dione <1996DEP4440193>. Cyclization of methyl 4-(alr-3,5-H-2-oxomorpholin-5-yl)butyrate in boiling toluene provided ar-4,9a-//-4-phenylper-hydropyrido[2,l-f][l,4]oxazine-3,6-dione <1995H(41)1931, 2000T233>. 

Perhydropyrido[l,2- ]pyrazin-l-one was prepared in the reaction of methyl pipecolinate and ethylene imine in boiling EtOH <19951JSP5461047>. Cyclocondensation of ethyl 2-amino-2-(2-pyridyl)acetate with DMAD, followed by treatment of reaction mixture with NaOMe, gave the 2-(l-methoxycarbonyl)-4-oxo-47/-pyrido[l,2- ]pyrazin-3-yl)acetate <1996JHC639>. 

Ugi five-center three-component reaction of pipecolinic acid and glycol aldehyde dimer with isocyanides gave a 1 1.7-2.1 diastereomeric mixture of l-oxoperhydropyrido[2,Tc][l,4]oxazine-9-carboxamides 397 (Scheme 35) <20010L4149>. Using CF3CH2OH as solvent is critical for the reaction. When 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid was employed, 1,3,4,6,11,11 a-hexahydro-[ l,4]oxazino[4,3+]isoquinoline-4-carboxarnide was formed. 

Optically active and deuterated pipecolinic acids were prepared via 4-phenyl-l,3,4,6,7,9a-hexahydro <2002JOC2424>, -perhydropyrido[2,l-f][l,4]oxazin-l-ones <1995TL1657, 1996JOC5736, 1996TL4001,... 

Reaction of the aldehyde-tethered furanone 244 with pipecolinic acid results in the formation of the oxazolopyr-idine derivative 245, which undergoes spontaneous decarboxylation to give the ylide 246. This in turn undergoes an intramolecular cycloaddition with the tethered exomethylene group to give 247, or with the endocyclic alkene to give the furoindolizine 248 <1997T10633> (Scheme 66). 

Some interesting fused 1,2,3-triazole ring systems have been reported. A series of 5-piperidyl-substituted 7-hydroxy-3f/-l,2,3-triazolo[4,5-d]pyrimidines 143 has been synthesized from pipecolinate esters, benzylazides, and cyanoacetamide <06CHE246>. 4-Alkylidene-5,6-dihydro-4//-pyrrolo-[l,2-c][l,2,3]triazoles 144 were prepared from alkylidenecyclopropanes via diiodogenation/Cu(I)-catalyzed 1,3-dipolar cycloaddition/intra-molecular Heck reaction sequence <06SL1446>. 6,6-Dimethyl-2-phenyl-4,5,6,7-tetrahydro-27/-benzotriazol-4-one 145 were prepared from A-(5,5-dimethyl-3-oxocyclohexenyl)-S,S-diphenylsulfilimine and... 

Pipecolines, m3 81 thru m3 83 1-Piperazinoethanol, hi29 1-Piperidinecarboxyaldehyde, f40 Piperonal, m250 Piperonyl butoxide, m252 cv.v-Piperylene, pi6 Pivaldehyde, d677... 

On the basis of a comprehensive ECD study of chiral 2-alkyl-substituted piperidines92, such as (S -a-pipecoline [(5 )-2-methylpiperazine, (5 )-102] and their TV-methyl derivatives [(5)-103] in ethanol, the sign of the strong, long-wavelength CE near 200 nm, shifted to... 

As in the case of the formation of an azepine (Scheme 43), Pro afforded a pyrrolo[l,2-fl]azepine 88, and pipecolinic acid afforded a pyrido[l,2-a]aze-pine 89 (80JHC1593). 

Electrolytic reduction using a lead cathode in 20% sulfuric acid converted pyridine a-carboxaldehyde to a mixture of 41% of a-picoline, 25% of a-pipecoline and 11% of 2-methyl-1,2,3,6-tetrahydropyridine [443]. 

The resulting 2,6-xylidide a-pipecolinic acid (2.2.5) is methylated to mepivacaine using formaldehyde with simultaneous reduction by hydrogen in the presence of platinum on carbon catalyst [15]. 

Enaminone 128 (Scheme 33) is obtained, together with an isomeric indo-lizine derivative, by flash vacuum thermolysis of aminomethylene Meldrum s acid derivative through intermediate ketene and delocalized azomethine ylide (85TL833). The thermally induced cyclization of semi-cyclic dienamines to afford, for instance, tricyclic 129 is also believed to start with an azomethine ylide (97JOC7744) the p-chlorophenyl substituent is essential for the reaction. Unstabilized ylide 130, on the other hand, is generated from pipecolinic acid and /1-phenylcinnamaldehyde by the decarboxylation method target base 131 is formed by 1,7-electrocycliza-tion and [l,5]-hydrogen shift (99J(P1)2605). 

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