ETHYL 6-METHYLPYRIDINE-2-ACETATE

METALATION OF 2-METHYLPYRIDINE DERIVATIVES ETHYL 6-METHYLPYRIDINE-2-ACETATE... 

Ethyl pyridine-2-acetate and ethyl 6-methylpyridine-2-acetate have previously been prepared by carboxylation of the lithio derivatives of a-picoline and lutidine, respectively. Use of ethyl carbonate to acylate the organometallic derivative avoids the intermediacy of the (unstable) carboxylic acid, and the yields are better. In the present procedure potassium amide is used as the metalating agent the submitters report that the same esters may be formed by metalation with sodium amide (43% yield) or with w-butyllithium (39% yield). The latter conditions also yield an appreciable amount of the acid (which decarboxylates). 

CHLOROCYCLOBUTANE, 51, 106 Mesitylene, cyanation, 50, 54 METHALATION OF 2-METHYLPYRIDINE DERIVATIVES ETHYL 6-METHYL-PYRIDINE-2-ACETATE, 52, 75 Metalation, directed, 53, 59 Methallyl alcohol, with phenyl-mercuric acetate to yield 2-methyl-3-phenylpropional-dehyde, 51, 17 METHALLYLBENZENE, 52, 115 7r-Methallylnickel bromide, 52, 115... 

Amino-6-methylpyridine was reacted with ethyl orthoformate in the presence of acetic acid at 80-110°C for 1.5 hr to give formimidate (305),... 

In contrast to these vapour-phase reactions, it has been reported that ketones and aqueous ammonia (or ammonium acetate) in an autoclave give less complex mixtures of pyridines. Crotonaldehyde gives 5-ethyl-2-methylpyridine (570) in up to 59% yield, methyl vinyl ketone gives 2,3,4-trimethylpyridine (571) rather than 2,3,6-trimethylpyridine 1,3,3-trimethoxybutane has been used in place of methyl vinyl ketone (49JA2629). In some cases reverse aldol reactions occur (for example with benzalacetophenone) giving unwanted products. A similar reverse aldol is responsible for the production of triarylpyridines (572) when benzalacetophenones are treated with formamide and ammonium formate (73JA4891). 

Alternatively the oxidation of 4 -(methylsulfonyl) acetophenone with S8 and morpholine produces the 2-(4-(methylsulfonyl)phenyl)acetic acid ethyl ester (xiv), which is condensed with 2-methylpyridine-3-carboxylic acid methyl ester by means of terf-butyl magnesium chloride in hot tetrahydrofurane to give the ketosulfone (ix). 

Seidel28 cyclized compounds (32) derived from the amides (31) with dimethylformamide dimethyl acetal to the 3-substituted 2-oxo-2H-pyrido-[l,2- ]pyrimidines (33) by heating in acetic anhydride. On this basis he corrected the conclusion of Antaki,29 who had assumed that by reacting 2-amino-4-methylpyridine and ethyl ethoxymethylenecyanoacetate, the 2-oxo-2//-pyrido[l,2-a]pyrimidine (33 R = 8-Me, R1 = OEt) was produced. The product was in fact the 4-oxo isomer (36 R = 8-Me, R1 = H, R2 = COOEt). 

Purification by column chromatography was carried out according to the following procedure silica gel (10 g) is added to the dried solution of crude product obtained from the work up, and the solution is concentrated by rotary evaporation to afford a free-flowing powder which is placed at the top of a column (4.5 cm diameter) of 40 g of silica gel (230-400 mesh) and eluted with 25% ethyl acetate/hexane (containing 1% triethylamine) to afford 1.47 g (71%) of methyl 5-methylpyridine-2-carboxylate as a pale yellow solid, mp 54-55°C. 

In the case of organochromium(III) complex intermediates obtained from glycosyl halides, work by Somsak and coworkers showed that their decay into glycals [75] is marked by the remarkable stability of the organometalic compounds in aqueous solutions. From the same group came the radically new concept of using zinc metal under aprotic conditions [76]. In brief, they proposed that acetylated glycosyl bromides be treated with zinc dust in the presence of A-heterocyclic bases (e. g., 4-methylpyridine or 1-methylimidazole) in a variety of aprotic solvents (i. e., benzene, ethyl acetate, tetrahydrofuran, acetone, dichloromethane) to afford the... 

Ethyl-2-picotine. 4-Ethyl-2-methylpyridine a-methyl-7-ethylpyridine 4 -ethyl -a -picoline a-collidine. C,-H N mol wt 121.18. C 79,29%, H 9.15%, N 11.56%. Prepd from 2-picoline and acetic anhydride in the presence of zinc dust H. Maier-Bode, 1. Altpeter, Das Pyridin und Seine Derivate (Halle, 1934) p 54 Ger. pat. 390,333. 

S-Ethyl-2 -picoline, S.Ethyl-l.methylpyiidine, aldehyde-collidine aldehydine 2-methyl-5-ethy[pyridine 5-ethyl-o -picoline 3-ethyl-6-methylpyridine. CeH,N mol wt 121.18, C 79.29%, H 9.15%, N H.56%. Prepd by heating acetaldehyde ammonia in a double vol of abs ale Ador, Bayer, Ann. 155, 297 (1870) by heating ammonia water and paraldehyde in presence of ammonium acetate Diirkopf,... 

In the synthesis of ( )-D-homoestrone (Scheme 7), Michael addition of the monoketal 42 of the Wieland-Miescher enedione to 6-vinyl-2-methylpyridine 41 led to tricyclic adduct 43 in good yield. Reduction to the 17a-P-alcohol, double bond hydrogenation, and ketalization produced 44 with the requisite 8 J,14a-stereochemistry in 58% yield. However, modification of the hydrogenation conditions from ethyl acetate-triethylamine to ethanol-perchloric acid raised the yield to 82%.Birch reduction, hydrolysis, cyclization, and ketal reversal... 

Betaines. a-Bromacrylic acid in ethyl acetate added dropwise to a soln. of 3-hydroxy-6-methylpyridine-2-thione in the same solvent, stirred and heated over-... 

In some early experiments, 3-picoline and 5-ethyl-2-methylpyridine were converted into 3-bromomethyl- and 5-a-bromoethyl-2-methylpyridine, respectively, by means of bromine in hydrochloric acid220a. With bromine in acetic acid, 4-picoline gives a tribromo-derivative which is not 4-tri-bromomethylpyridine22i. 2- and 4-Phenacylpyridine222 and ethyl 2-pyri-dylacetate223 are easily monobrominated in the methylene groups. 

The formation of imidazopyridines is known to be a two-step process. It was shown earlier [46] that the first step in the reaction - the alkylation of 2-aminopyridine with bromomethyl (adamantan-l-yl) ketone was successfully carried out with a high yield of l-[3-adamantan-l-yl)-2-oxoethyl]-2-amino-pyridinium bromide 29a by boiling the reagents for 1 h in ethanol or ethyl acetate. They have established that the introduction of an electron-acceptor substituent into the pyridine ring, considera-bly hinders the reaction. When 2-aminopyridine, 2-amino-4-methylpyridine, or 2-amino-3-methylpyridine were heated with bromomethyl(adamantan-l-yl) ketone in ethyl acetate for 1 h, the yields of compounds 29a, 52a, 56a varied within the limits of 80-95% and, whereas with 2-amino-6-bromo and 2-amino-5-chloropyridine the corresponding alkylation products - compounds 49a, 57a were obtained in yields of only 50%. In the case of 2-amino-5-bromo-3-trifluoromethylpyridine, the formation of only a negligible amount of compound 58a was observed after 1 h and the yield reached 42% only after 5 h... 

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