Orthoformic acid, ethyl ester, reaction with

The synthesis of the moxifloxacin core (de Souza, 2006 Martel et al., 1997 Seidel et al., 2000) proceeds from a Grohe-Heitzer sequence as described earlier in the chapter. Unlike the traditional Grohe-Heitzer sequence, however, the opening step involved the reaction between acid chloride 101 with the mono potassium salt of malonic acid monoethyl ester (102) in the presence of triethylamine to deliver ketoester 103 (Scheme 4.18). Treatment of 103 with ethyl orthoformate furnished acrylate 104, which reacted with cyclopropyl amine to afford 105. Cyclization of 105 in the presence of sodium fluoride in DMF gave the moxifloxicin core 106. 

Esterification of sulfonic acids.1 Sulfonic acids are converted into methyl or ethyl esters on reaction with trimethyl or triethyl orthoformate. Yields are >80% in esterification of arenesulfonic acids, but are somewhat lower in the reaction of alkanesulfonic acids because of volatility of the products. 

The treatment of di- or triacetyl-D-pseudoglucal with methanol and hydrogen chloride produces mixtures of methyl cycloacetals (glycosides).18 By the reaction of the diacetate with the ethyl ester of orthoformic acid, a crystalline ethyl diacetyl glycoside (XXVII) was obtained.18 By... 

Baker and Boyce [122] determined isomers of toluenesulphonic acid as ethyl esters prepared by the reaction with triethyl orthoformate. About 0.1 ml of sulphonic acid was added to a known amount of toluene (12 ml) and the water produced was removed by azeotropic distillation with about 5 ml of toluene. o-Terphenyl (0.05 g in 3 ml of toluene) was added as an internal standard, followed by a 20-fold excess of triethyl orthoformate, and the solution was refluxed for 15 min. After this period the reaction proceeds quantitatively and the reaction mixture can be injected directly into the chromatograph. The separation was carried out on 3% of OV-101. 

Acetals and ketals are readily prepared from carbonyl compounds and orthoformic esters in alcohol solution in the presence of a catalyst such as concentrated sulfuric acid, anhydrous hydrogen chloride, or ammonium chloride (60-95%)/ The reaction mixture must be neutralized before processing since the acetals are very sensitive to an acid hydrolysis. The methyl and ethyl esters of orthosilicic acid have been substituted for the ortfioformic esters with good results (70-90%) however, steps must be taken to remove compounds of silicon. ... 

Acetals and ketals having a second junctional group ate made by these procedures. For example, acrolein reacts with ethyl orthoformate in alcohol solution with ammonium nitrate as catalyst to give acrolein diethyl acetal (73%). On the other hand, it reacts with ethyl ortho silicate with anhydrous hydrogen chloride as catalyst to furnish (i-ethoxypropionaldehyde diethyl acetal (76%). p-Bromoacetophenone and ethyl orthoformate give the corresponding ketal in 65% yield. p-Methoxy- and m-amino-benzaldehyde diethyl acetals are made in a similar way in 96% and 85% yields, respectively. a-Keto esters like ethyl a-keto-n-butytate and ethyl a-keto-tr-valetate are converted to their diethyl ketals in excellent yields by the action of orthoformic ester in ethanol-hydrochloric acid solution. If the reaction is carried out in the presence of ethylene glycol instead of ethanol and, in addition, the volatile products are removed by distillation, then the ethylene ketal is formed in almost quantitative yield (cf. method 133). 

Similarly, 3-amino-4(3//)-quinazolinones (600) are formed in high yields when methyl or ethyl o-acylaminobenzoates are heated with hydrazine in an alcohol. Alternatively, acylation and cyclization of an o-aminobenzoylhydrazine is effected by heating with anhydrous formic acid, ethyl orthoformate, or acetic anhydride. Related is the action of heat on a mixture of anthranilic esters and semicarbazides to yield A3-aminated 2,4(1//,3//)-quinazolinediones (601). Reactions which involve... 

Condensation of the Grignard complex of 58 with triethyl orthoformate (59) gave a 75% yield of distilled hydroxyacetal 60. Partial hydrogenation of 60 to 61, followed by acidic hydrolysis, provided hydroxyaldehyde 62, which was isolated in the (all- -configuration. A Wittig reaction of 62 with the ylide of (a-ethoxycarbonylethyl)-tris(dimethylamino)-phosphonium bromide (63) furnished the hydroxyester 64. Treatment of 64 with ca. 0.5 mol equivalents of PBr3 in ether/hexane at -5°C in the presence of a small amount of pyridine gave an 84% yield of crystalline ester bromide 65, which could be transformed to the phosphonium bromide 55 (yield 93%) by reaction with triphenylphosphine in ethyl acetate. 

This acetylpyridone diester 15 was conveniently synthesized in 60% yield by reacting acetoacetamide with ethoxy-methylene oxalacetic acid diethyl ester 14 in ethanol in the presence of sodium acetate (13). Compound 14 was prepared according to the procedure of R. G. Jones by condensing ethyl oxalacetate with ethyl orthoformate in the presence of acetic anhydride (14). It was found that purified compound 14 gave the best yield (60%) of acetylpyridone diester 15, but as a matter of convenience, crude 14 gave product 15 in up to 40% yield. Isolation of 15 was expedited by the precipitation of its sodium salt from the reaction mixture. 

Saloutin et al. reported [138] that the self-condensation of ethyl pentafluorobenzo-ylacetate (271) on refluxing without any catalyst leads to the formation of compound 272 in 37 % yield, acid hydrolysis of which gave 2-pentafluorobenzoyhnethyl-5,6,7,8-tetrafluorochromone (273). Other routes for preparing some new ring-fluorinated chromones have been performed from the 2-ethoxymethylene pentafluorobenzo-ylacetic ester (274) and also via intramolecular cyclization of ethyl pentafluoroben-zoylpyravate (275). The reaction of ester 271 with ethyl orthoformate results in the... 

Regiochemical synthesis of 1-substituted imidazole-4-carboxylates can be achieved by treatment of a (Z)-)3-dimethylamino-of-isocyanoacrylate with an alkyl or acyl halide (see Section 2.1.1 and Scheme 2.1.8), by cyclization of 3-alkylamino-2-aminopropanoic acids with triethyl orthoformate followed by dehydrogenation of the initially formed imidazoline (see Section 3.1.1 and Scheme 3.1.2), by condensation of 3-arylamino-2-nitro-2-enones with ortho esters in the presence of reducing agents (see Section 3.1.1 and Scheme 3.1.4), by reaction of an alkyl A -cyanoalkylimidate with a primary amine (see Section 3.2 and Scheme 3.2.1), the poor-yielding acid-catalysed cyclization of a 2-azabutadiene with a primary amine (see Section 3.2 and Scheme 3.2.3), the cyclocondensation of an isothiourea with the enolate form of ethyl isocyanoacetate (see Section 4.2 and Scheme 4.2.5), and from the interaction of of-aminonitrile, primary tunine and triethyl orthoformate (see Chapter 5, Scheme 5.1.5, and Tables 5.1.1 and 5.1.2). 

The di-O-tosylates (prepared by action of tosyl chloride in pyridine) are reduced with zinc (Nal/Zn route e Tipson-Cohen reaction) [13]. Cyclic ortho-esters (prepared by reaction of the diol with ethyl orthoformate) are transformed into olefins by simple heating in the presence of acids (Eastwood reaction, route b) [14]. Cyclic thiocarbonates (obtained by reaction of a diol with thiophosgene or (V,(V -thiocarbonyl-di-imidazole) are reduced to olefin with trimethyl phosphite (Corey-Winter method, route c) [15]. Finally, reduction of vicinal di-xanthates with tri- -butyltin hydride according to the Barton procedure [16] affords olefins via a reductive elimination process route a). The Corey-Winter, Garegg, and Tipson-Cohen methods are most commonly applied for deoxygenation of sugar diols. 

Many communications have concentrated on specific amino phosphonic acids or derivative types. Thus, esters of phosphonoaminoacetic add were obtained by the reactions between trialkyl (ethyl) phosphite and (218) and which are thought to proceed via the phosphorane (219). A sequence has been presented for the preparation of the mono- and di-benzyl esters of N-chz protected (a-aminoben-zyl)phosphonic acid. A synthesis of (aminomethylene)bisphosphonic acid from dibenzylamine, dibenzyl hydrogenphosphonate and triethyl orthoformate has been noted and the asymmetric hydrogenation of (220) in the presence of chiral phosphine catalysts yields samples of (221) with e.e.s of 63-96%. The pyrrolidine-based compound (222) has been prepared from methyl S)-N-methoxycarbonyl-4-oxo-2-pyrrolidinecarboxylate and iV-coupled 4-amino-butanal diethyl acetals were the starting materials in syntheses of the pyrrolidine-2-phosphonic add derivatives (223) in which Z represents the iV-protected amino add or peptide moiety. ... 

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