Pyridine, 2-amino-, reaction with ester

The Zincke reaction has also been adapted for the solid phase. Dupas et al. prepared NADH-model precursors 58, immobilized on silica, by reaction of bound amino functions 57 with Zincke salt 8 (Scheme 8.4.19) for subsequent reduction to the 1,4-dihydropyridines with sodium dithionite. Earlier, Ise and co-workers utilized the Zincke reaction to prepare catalytic polyelectrolytes, starting from poly(4-vinylpyridine). Formation of Zincke salts at pyridine positions within the polymer was achieved by reaction with 2,4-dinitrochlorobenzene, and these sites were then functionalized with various amines. The resulting polymers showed catalytic activity in ester hydrolysis. ... 

A solution of a 2-aminobenzophenone (0.1 mol) and an z-amino acid ethyl ester hydrochloride (0.15 mol) in pyridine (200 mL) was refluxed. During the first 4h, 20-50 mL of liquid was allowed to distill and was replaced by fresh pyridine. Heating was continued for a further 11 h, the mixture was evaporated under reduced pressure and H20 and Et20 were added. In most cases some of the reaction product remained undissolved and was filtered off. The aqueous layer was separated, made alkaline and extracted with Et20. The comhined F.t20 phases were washed with H20. dried and evaporated and the reaction product was separated from unchanged amino ketone by crystallization. 

Reactions of methyl nitroacetate with aldehydes are induced by TiCl4 in pyridine. They afford nitroalkenyl-esters,64 which are used in the preparation of various nonnatural amino acids (Eq. 3.39).65... 

Activated esters of A-alkoxycarbonylamino acids are prepared by two approaches, activation of the acid followed by reaction with the hydroxy compound, and trans-esterification. Most of the products are stable enough to be purified by washing a solution of the ester in an organic solvent with aqueous solutions. A few that are not crystalline are purified by passage through a column of silica. The commonly used method for their preparation is addition of dicyclohexylcarbodiimide to a cold mixture of the reactants in dimethylformamide or ethyl acetate. The first Boc-amino acid nitrophenyl esters were obtained using pyridine as solvent. Pyridine generates the nitrophenoxide ion that is more reactive. For one type of ester, 2-hydroxypyridino... 

FIGURE 7.13 Preparation of an Fmoc-amino-acid pentafluorophenyl ester by reaction of the acid with pentafluorophenyl trifluoroacetate in the presence of pyridine.32... 

The alternative method for making activated esters is base-catalyzed transesterification. Fmoc-amino acids are esterified in excellent yields by reaction with pentafluorophenyl trifluoroacetate at 40°C in the presence of pyridine (Figure 7.13). A mixed anhydride is formed initially, and the anhydride is then attacked by the pentafluorophenoxy anion that is generated by the pyridine. Succinimido, chlorophe-nyl, and nitrophenyl esters were made by this method when it was introduced decades ago. A unique variant of this approach is the use of mixed carbonates that contain an isopropenyl group [Cf C CfyO-COjR]. These react with hydroxy compounds in the presence of triethylamine or 4-dimethylaminopyridine (see Section 4.19) to give the esters and acetone.30 35... 

Peptide synthesis. Dipeptides can be obtained in moderate yield by reaction of an N-protected amino acid with SiCl4 in pyridine followed by addition of an amino acid ester. However, racemization is extensive and the Cb-protective group is not stable under the reaction conditions. 

Polymer-bound isonitrile (423), obtained from TentaGel-NH2 through treatment of the resin with formic acid and acetic anhydride, followed by dehydration of the resulting formamide with tosyl chloride and pyridine, has been employed in the preparation of N-substituted amino add ester [349]. Thus, Ugi MCR, performed in the presence of an alcohol instead of the carboxylic component, gave rise to an imino-ether spedes (426). Several Lewis acids were tested in searching for optimal reaction conditions. Boron trifluoride etherate displayed the better yields in term of desired product of the Ugi-type reaction. Amino acid methyl esters (427) were thus obtained when using methanol as the alcohol component, after deavage from the resin of the intermediate imino-ethers by an acetone/water mixture (Scheme 87). 

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