Ethyl-2-azidoacetate

Cyclization of substituted vinylic imidazo[l,2-tf]pyridines has been used to synthesize angular tricyclic systems. For example, reaction of 136 with ethyl azidoacetate 137 to give 138 followed by cyclization furnishes 139 (Scheme 10) <2001JOC6576>. 

To a solution of 1.84 g Na metal in 60 ml ethanol at 5-10° add, over Vi hour with vigorous stirring a mixture of 0.08 M ethyl azidoacetate and 0.02 M 2 (or 2,5 2,3 etc. but not 6) substituted benzaldehyde and continue stirring at 5-10° until nitrogen evolution ceases (about V2-I hour) then stop immediately and rapidly evaporate in vacuum Vi the ethanol (keep temperature below 30°). Basify the solution with solid NH CI, dilute with 500 ml water and extract 3 times with ether. Filter, wash with water to neutrality and dry, evaporate in vacuum the ether (or can dissolve the residue in petroleum ether, or 1 1 petroleum ether.benzene for methoxy compounds, and filter through silica gel) to get the ethyl-alpha-azidocinnamates (1) in about 50% yield. Store in freezer until used in next step. Dissolve 1 g (I) in 100 ml p-xylol and reflux 10 minutes. Evaporate in vacuum (or add 5 ml pentane, filter, evaporate in vacuum) to get about 90% yield of the 4 substituted-2-car-bethoxyindole which can be decarboxylated as described elsewhere here. 

Ethyl acetate Azide, Ethyl azidoacetic Acid or Azidoacetlc Acid Ethyl Ester, N3CH2.CX>.OC2H5 ... 

Azidoethylazidoacetate (Triazoethyl Triazoacetate). See under Ethyl azidoacetate and Beil 2, 229... 

In the [2,3-6]-fused pyrrole series, ethyl azidoacetate could only be condensed with 2-ethoxycarbonyl-4-formylpyrrole (223) to yield an azidodiester (224) thermolysis of which gave 2,5-diethoxycarbonylpyrrolo[2,3-6]pyrrole (225). Hydrolysis and subsequent... 

Peptides. A new amide or peptide synthesis is based on the formation of iminophosphoranes, R N=PR3, from the reaction of azides with a tertiary phosphine. These phosphoranes react with carboxylic acids to form amides.1 Ethyl diphenylphosphinite is more useful than a triarylphosphine because the by-product is hydrolyzed to diphenylphosphinic acid, which can be readily removed. The iminophosphorane 2, derived from 1 and ethyl azidoacetate, reacts with CboGly-L-Phe-OH to give optically pure 3 in 70% yield.2... 

Compounds (21) and (23) have been synthesized from ethyl azidoacetate and thiophene-2,3-dialdehyde (80). Blocking one formyl group ultimately led to the corresponding pyridone derivatives. Overall yields are approximately 40% for each reaction sequence (Scheme 29) <76CJC1066>. 

Thermolysis of the azide (434), prepared by treatment of the aldehyde (433) with ethyl azidoacetate in base, at reflux in xylene furnishes the pyrazolo[3,4-c]pyridine (435) (22%) along with the aldehyde (433) (Scheme 50) <84JCS(P1)2189>. Attempts to facilitate the reaction by addition of iodine did not increase the yield. These yields are somewhat lower than reported earlier <79CC627>. 

Aryl-4-chloromethylselenazoles (72) are hydrolyzed to alcohols (73). Manganese dioxide oxidation of (73) affords 4-formyl derivatives (74) which by condensation with ethyl azidoacetate give azidocrylates (75). Thermal cyclization of compounds (75) give pyrrolo[3,2-d]selenazoles (76 Scheme 27) (79JHC1563). 

Scheme 1.7. Regioselective addition of ethyl azidoacetate to an azahomo[60]fullerene derivative followed by extmsion of dinitrogen.

Sodium (0.600 mol) was dissolved in 400 ml 100% ethyl alcohol then cooled to -10°C. This was then treated with a mixture of the Step 1 product (0.150 mol) and the dropwise addition of ethyl azidoacetate (0.558 mol) dissolved in 100 ml diethyl ether, while the reaction remained -10°C. The mixture was warmed to 20°C over 3 hours, then poured into 700 ml water, and extracted twice with diethyl ether. The ethereal solution was washed with water, brine, then dried with Na2S04, and concentrated. After cooling, the residue was cooled to -10°C for 24 hours and a solid was isolated. The solid was washed with hexanes, filtered, and the filtrate reconcentrated. The residue was purified by chromatography with silica gel using EtOAc/hexane, 5 95, and the product isolated in 53% yield as an yellow crystalline material, mp = 64-66°C. 

Ethyl cyanoformate is an effective dipolarophile undergoing 1,3-dipolar addition to azides, for example with ethyl azidoacetate to afford tetrazoleacetic acid derivatives (Ref. 45). Tetrazoleacetic acid is a key starting material for the preparation of pharmaceuticals such as the antibiotic Cefazolin [Scheme 48],... 

An alternate route for the annelation of a pyrrole ring employs the base-catalyzed condensation of furan-, thiophene-, and selenophene-carbox-ald ydes with ethyl azidoacetate the bicyclic products are indole Isoster-es. The Isomeric (3,2-b)pyrroles can be similarly prepared from the corresponding 2-carboxaldehydes. 

Thermolysis of azidoacrylate (519) obtained by condensation of the appropriate benzo[Z>]furan-2-carbaldehyde (518) with ethyl azidoacetate afforded the corresponding alkyl benzo[Z ]furo[3,2-Z ]pyrrole-2-carboxylates (520) with 61% overall yield (Scheme 42) <82CCC3288>. 

A general synthesis of c-fused pyridines under neutral conditions involves the thermolysis of vinyl azides, prepared from aromatic aldehydes that bear an ortho methyl group and ethyl azidoacetate. Thus thermolysis of the vinyl azide (151) from mesitaldehyde (150) gives the isoquinoline (152) in 45—50% yield (Scheme... 

In 1992, Molina et al. synthesized partial structures of lavendamycin using the aza-Wittig reaction as the main strategy (68) to form a /3-carboline at the 2-position of a quinoline (Scheme 23) (68). The reactions of the iminophosphorane 194, prepared from 3-formyl-l-methyl indole by treatment with ethyl azidoacetate and triphenylphosphine, with the 2-formyl-quinoline derivatives 195 in toluene at 160°C in a sealed tube gave the corresponding quinoline derivatives 196 and 197. Treatment of iminophosphorane 194 with pyruvaldehyde yielded the key j3-carboline intermediate 198, which was reacted alternatively with the 2-aminobenzaldehyde 199 and JV-(0-formylphenyl)triphenyliminophosphorane 200 to obtain the corresponding partial structures of lavendamycin, 201 and 202, respectively. 

Thermal decomposition of azidoacrylates, which were prepared by condensation of ethyl azidoacetate with heteroaromatic aldehydes, produced a series of the previously unknown fused heteroaromatic analogues of isoellipticine 291 (98HEC227). 

In this reaction, the starting materials are usually prepared by the Claisen-Schmidt Condensation between aromatic aldehydes and methyl azidoacetate for example, upon treatment with 4 eq. ethyl azidoacetate and sodium methoxide in methanol, the corresponding azidocinnamic ester was prepared from 2-0-(T-methyl)hexyl-5-bromo 2-hydroxylbenzaldehyde. On the other hand, the thermal decomposition is usually carried out in refluxing xylene,yielding indole derivatives of highly regiospecificity." ... 

To a 0.15 M NaOEt (4 eq.) solution in ethanol at 0°C was added dropwise a solution of 1 eq. 3-formylthiophene and 4 eq. ethyl azidoacetate. The resulting mixture was stirred at 0°C for 1 h and at room temperature for an additional 1 h then it was poured into a saturated NH4CI solution. The product was extracted with ether, and the combined organic layers were dried over Na2S04 and concentrated in vacuo. The residue was purified by silica gel column chromatography to provide ethyl o -azido-j5-(3-thiophenyl) acrylate. 

A mixture of 4.15 g ethyl azidoacetate (32 mmol) and 1.1 g 3-formyl-4-methoxypyridine (8.02 mmol) in 50 mL anhydrous EtOH was added dropwise under nitrogen at -15" C to a 30 mL well-stirred solution containing 0.74 g Na (32.1 mmol). The mixture was stirred at -15°C for 72 h and poured into 50 mL 30% NH4CI aqueous solution. The separated solid was washed with H2O, air-dried, and recrystallized from EtOAc/n-hexane (1 1) to give 1.21 g ethyl Qf-azido-)0-(4-methoxypyrid-3-yl)-acrylate as colorless needles, in a yield of 61%, m.p. 106-108°C. 

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