With ethyl orthoformate

Acrolein Acetal (ir, i) By treating acrolein with ethyl orthoformate in the presence of ammonium nitrate. Fischer and Baer, Helv. Chim. Acta i8, 514 (1935). 

Ethoxy-2-cyclohexenone has been prepared by reaction of the silver salt of dihydroresorcinol with ethyl iodide and by the reaction of dihydroresorcinol with ethyl orthoformate, ethanol and sulfuric acid." The acid-catalyzed reaction of dihydroresorcinol with ethanol in benzene solution utilized in this preparation is patterned after the procedure of Frank and Hall. ... 

In the sjmthesis of evodiamine effected by Asahina and Ohta,i N-methylanthranilic acid was converted by ethyl chloroformate into N-methylisatoic anhydride, which, on treatment with 3- -aminoethylindole, furnished 3-/3-o-methylaminobenzoylaminoethylindole (III), and this with ethyl orthoformate at 175-180° gave dZ-evodiamine, m.p. 278°, convertible by boiling alcoholic hydrogen chloride into Zsoevodiamine, m.p. 147°, as shown above. 

In cases where decarboxylation is anticipated, the quinazolinone could be obtained by heating ammonium o-formamidobenzoate or o-forra ami do benz amide for several hours. This ring closure could be effected more conveniently by boiling the o-formamidobenzamide with 3% aqueous sodium hydroxide for a few minutes, o-Amino-benzamides have also been converted to quinazolinones by refluxing with ethyl orthoformate alone or preferably in the presence of acetic anhydride. ... 

The methiodide and ethiodide of 4-methylcinnoline possess methyl groups which condense easily with aldehydes, and even with ethyl orthoformate,to give polymethine derivatives. These reactions, particularly that with the ortho ester, suggest that the salts have structure 55 (R = Me or Et, R = Me). The methiodide of 3-methylcinnoline also reacts with aldehydes, although more slowly, but no reaction with ethyl orthoformate has been reported. Although 55 (R = Me) appears to be the most likely structure for the product, the 4-methyl group may direct the quatemization on and,... 

An electrophile can be introduced into the N-2 position of 3-hydroxyfurazans 258 via their 0-trimethylsilyl intermediates (e.g., 259). A 1 1 mixture of/V- (260) and 0-alkylation (261) products was formed on heating 259 with ethyl orthoformate (93T5905) (Scheme 169). 

Halogenation of the 7 position also proves compatible with good antiinflammatory activity. Construction of this compound, aclomethasone dipropionate (80), starts by introduction of the required unsaturation at the 6,7 position by dehydrogenation with DDQ (76). The highly hindered nature of the hydroxyl at position 17 requires that a roundabout scheme be used for formation of the corresponding ester. Thus treatment of 76 with ethyl orthoformate affords first the cyclic orthoformate This then rearranges to the 17 ester on exposure to acetic acid. Acylation of the 21 alcohol is accomplished in straightforward fashion with... 

Grignard reaction, (Continual) with ethyl formate, 16, I r with ethyl orthoformate, 16, 41 with water, 11, 84... 

The synthesis of the corresponding naphthyridone scaffold was carried out according to the methods reported by Chu et al. [12] and Sanchez et al. [13]. Namely, the hydrolysis of ethyl 2,6-dichloro-5-fluoronicotinate (3) [14] followed by reaction with thionyl chloride results in the formation of 2,6-dichloro-5-fluoronicotinyl chloride (4). Treatment of this compound with monoethyl malonate in THF under n-butyllithium followed by acidification and decarboxylation gives rise to ethyl 2,6-dichloro-5-fluoronicotinylacetate (5). Reaction of compound 5 with ethyl orthoformate in acetic acid followed by cyclopropylamine results in the formation of 3-cyclopropylamino-2-(2,6-dichloro-5-fluoronicotinyl)acrylate (6), the cyclization reaction of which under NaH/THF gives rise to the required ethyl l-cyclopropyl-6-fluoro-7-chloro-l,4-dihydro-4-oxo-l,8-naphthyridine-3-carboxylate (7), as shown in Scheme 3. 

The synthesis of compound 27 was initiated with the treatment of ke-toester 29, reported by Yoshida et al. [25], with ethyl orthoformate in acetic acid, followed by reaction with (l.R,2S)-2-fluoro-1-cyclopropylamine p-toluenesulfonic acid salt in the presence of triethylamine to yield an enam-inoketoester intermediate, cyclization of which under NaH in dioxane yields the 5-nitroquinolone derivative (30). Reduction of the nitro group of compound 30 followed by acid hydrolysis provides compound 27 via the amino-quinolone derivative (31), according to Scheme 7. 

Anilines were first reacted with ethyl orthoformate to give N,N -diarylformamidines, which were then treated with a second batch of ethyl orthoformate and diethyl malonate in the presence of ZnCI, to afford arylaminomethylenemalonates (251) (86M1P1). 

The uncatalyzed reactions between anilines, ethyl orthoformate, and diethyl malonate afforded ethyl arylaminomethylenemalonamates (252) in 67-85% yields (87SC549). However, if the malonate was first reacted with ethyl orthoformate and acetic anhydride in the presence of a catalytic amount of ZnCl2 at boiling temperature for 5 hr and aniline was then added to the reaction mixture, reflux being maintained for 0.5 hr, arylaminomethylenemalonates (253) were obtained in 52-85% yields. 

Arylazo-l-naphthylamines were first reacted with ethyl orthoformate in boiling xylene for 2 hr diethyl malonate and piperidine were then slowly added to the reaction mixture over a period of 15-20 min. The resulting... 

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),... 

Anilines, bis(2-amino-4-chlorophenyl)disulfide, naphthylamine, 2- and 3-aminopyridines, 2-aminopyrimidines, 2-, 3-, 5-, 6-, 7-, and 8-aminoquino-lines, 6-aminocoumarin, and 2-aminopyrazine were reacted in the absence or presence of a solvent (ethanol, toluene) with ethyl orthoformate and isopropylidene or 4-heptylidene malonates to give alkylidene (het)aryl-aminomethylenemalonates (442, R = R2 = Me, Pr) in 32-100% yields [69BRP1147759 75USP3907798 88JAP(K)239269]. p-Toluenesulfonic acid monohydrate was sometimes applied as catayst. 

Furthermore, the homologous complex 286 condenses with ethyl orthoformate to give, in the course of a new y-tropolone synthesis, tropolone ether 287 by O-ethylation it is transformed to tropylium salt 288 (Scheme 72 70JA6382) the corresponding tropone complex was synthesized from dibenzotroporic and Cr (CO)6 [83AG(S)734]. 

Acetyluracil — Ethyl 2-hydroxy-4-methyl-5-pyrimidinecarboxylate (XXXVI), which is prepared by the cyclization of the ureidomethylene derivative of aceto-acetic ester, can be caused to rearrange into 5-acetyluracil (XXXVII) in dilute alkali [304]. Compound (XXXVII) can also be prepared from diketene and ethyl carbamate, followed by treatment with ethyl orthoformate and cyclization with ammonia [305]. 

Cyclization of 167 with ethyl orthoformate leads to 176 (R = H, 36%). With cyanogen bromide in refluxing methanol 176 (R = NH2) is obtained in only 10% yield. Reaction of 167 with carbon disulfide (methanol, H2O, KOH, reflux) leads to the 5-methylthiazolo[3,2-6][l,2,4]triazole-2-thiol (176, R = SH), which was readily converted to 176 (R = SMe) with methyl iodide [76JHC(13)1225]. 

The parent compound 309 was synthesized by the reactions of cis- or rra i-2-amino-l-cyclohexanecarboxamides with ethyl orthoformate [69-JCS(C)1635 71JCS(C)238]. In principle, 309 can exist in five tautomeric forms two enol forms, one lactim form, and the IH and 3H forms, of which the two enol forms can be excluded because no cis-trans isomerization was observed. The H and 3H forms may be fixed with substituents hence, 310 and 311 with fixed tautomeric structures were prepared. The UV spectra reveal that the unsubstituted derivatives exist in 3H form, as shown for structure 309 [71JCS(C)238]. 

Reacting this with ethyl orthoformate gives a methoxymethylene derivative... 

The iminohydrazine (128) reacts with ethyl orthoformate to give the triazoloazepine (129) (Equation (50)) <86H(24)907>. 

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. 

Treatment of the hydrazide 59 with ethyl orthoformate causes an intramolecular N-acylation resulting in the tetracycle 60. The conversion of 1,4-diphenylcarbazole into 61 using N-methylformanilide-phosphorus oxychloride at 95°C must involve an oxidation at some stage. Heating car-bazole with diphenyl 2-benzylmalonate, diethyl 2-ethylmalonate, or malonic acid-phosphorus oxychloride produced the tetracycles 62 (R = PhCH2, Et, and H, respectively). It is not clear whether the N-9 or the C-1 acylations required for the formation of 62 occur first, although it is likely that the initial attack is at the nitrogen. 

Condensation of 2-mol equivalents of 9-aminocarbazole with ethyl orthoformate-boron trifluoride yielded the formamidine 127, which was oxidized with lead dioxide to the spectrally observable radical 128 in solution. ... 

Closely related are the cyanine dyes, for example cyanine (62) itself, which is formed from the ethiodide salts of lepidine and 4-iodoquinoline in the presence of base (Scheme 51). Analogous monomethine cyanines can have the quinoline nuclei linked 2,2 (pseudocyanines) and 2,4 (isocyanines). Quinaldine ethiodide on condensation With ethyl orthoformate gives the 2,2 -linked trimethine cyanine (carbocyanine) (63), known as pinacyanol (Scheme 51). 

Reaction of 104 with ethyl orthoformate affords 105, which gives a mixture of 57% 106 and 36% 107 upon treatment with ammonia in methanol. When alkylamines are used, 6-alkylaminopyrazolo[3,4-d] pyrimidines are produced they are formed via a Dimroth rearrangement of 5-aIkyl-4-iminopyrazolo[3,4-d]pyrimidine (80JA3897). Reaction of 104 with ethyl orthoformate, followed by HjS, gives 3-cyano-4-mercaptopyrazolo[3,4-d]-pyrimidine (84KGS253). 

Cyclization of the hydroxamic derivative 127 with ethyl orthoformate gives the pyrazolo[3,4-d] pyrimidines 128 (74GEP2356690). 

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