Methoxy- and Ethoxycarbonyl

The instability of /er/-butyl chloroformate limits its use for preparing Boc derivatives. rm-Butyl fluoroformate (bp 40-42 C/23.3 kPa) is more stable than the chloro derivative and more reactive than /err-butyl azidoformate (HAZARD). Both reagents should be prepared afresh. re/t-Butyl azidoformate (bp 36.5-37.5 C/1.3 kPa) has the added frisson of being explosive hence, it should be prepared in situ from the reaction of Boc-hydrazide with nitrous acid and used without purification. Moreover, the by-product of aqueous workup, hydrazoic acid, is highly toxic. 

---

The early use of aqueous potassium hydroxide in acetone for the acetylation and benzoylation of 3-nitrocarbazole using the acid chlorides has been subsequently repeated for the N-acetylation of 3,6-dinitrocarbazole with acetic anhydride, for the N-acetylation, ethoxycarbonylation, 4-fluorobenzoylation, and prop-2-ynoylation of 2-nitrocarbazole and for the methoxy- and ethoxycarbonylation of carbazole itself utilizing the chloroformate esters. 

The base-catalyzed reaction of benzyl cyanides with p-chloronitro-benzenes is widely used as a preparative route to 3-arylanthranils (Eq. 8), and hence, by reductive ring opening, o-aminobenzophenones, the valuable precursors of the pharmacologically important benzodiazepinones. By this method 3-phenylanthranils bearing trifluoromethoxy,173 (trifluoromethyl)-thio,173 sulfonamido,174 methoxy- and ethoxycarbonyl,175,176 cyano,175 methylsulfonyl,175 halo,176 difluoromethoxy,177 and acetyl (protected as the... 

Methoxy- and ethoxycarbonyl Alkaline hydrolysis under vigorous conditions, or with powerful nudeophiles such as thiolates... 

When large groups, such as phenyl, bromo, ethoxycarbonyl or nitro are attached at position 3, the principal products are l-alkylcinnolin-4(l/f)-ones. Cyanoethylation and acetylation of cinnolin-4(l/f)-one takes place exclusively at N-1. Phthalazin-l(2/f)-ones give 2-substituted derivatives on alkylation and acylation. Alkylation of 4-hydroxyphthala2in-l(2/f)-one with an equimolar amount of primary halide in the presence of a base leads to 2-alkyl-4-hydroxyphthalazin-l(2/f)-one and further alkylation results in the formation of 4-alkoxy-2-alkylphthalazinone. Methylation of 4-hydroxy-2-methyl-phthalazinone with dimethyl sulfate in aqueous alkali gives a mixture of 4-methoxy-2-methylphthalazin-l(2/f)-one and 2,3-dimethylphthalazine-l,4(2//,3//)-dione, whereas methylation of 4-methoxyphthalazin-l(2/f)-one under similar conditions affords only 4-methoxy-2-methylphthalazinone. 

Treatment of 8-[(4-cyanophenyl)methoxy]-7-formyl-2-cyclopentyl-2,3,4,6,11,1 la-hexahydro-l//-pyrazino[l,2-i]isoquinoline-l,4-dione with (Et0)2P(0)CH2C00Et and NaH in THF at 40 °C overnight, or with (2-pyridylmethyl)-, 4-[(ethoxycarbonyl)benzyl]-, (4-nitrobenzyl)-, and (meth-oxymethyl)triphenylphosphonium halogenide in the presence of KH in THF at room temperature gave 7-ethylene derivatives 386 (98MIP7). 

The comparison between the cycloaddition behavior of simple diazoketones and of ethyl diazopyruvate 56 towards the same olefin underlines the crucial influence of the ethoxycarbonyl group attached to the carbonyl function. This becomes once again evident when COOEt is replaced by an acetal function, such as in l-diazo-3,3-di-methoxy-2-butanone 86 with enol ethers and acetates, cyclopropanes rather than dihydrofurans are now obtained 113). ... 

A Japanese group have been investigating the use of readily accessible dihydrocinnoline derivatives of the type 1 (R = alkyl, aryl, styryl, ethoxy X = H or methoxy) as novel precursors for the synthesis of other types of heterocycles. The following synthesis of 2-acetyl-3-cyanoindole is representative of a new general method (22-88% for 10 examples) for the preparation of 2-acyl- and 2-ethoxycarbonyl-3-cyanoindoles from 1 a mixture of 1 (R = Me, X = H 1 eq.) and powdered potassium cyanide (2 eq.) was stirred overnight in aqueous DMF at room temperature. Addition of water to the reaction mixture precipitated 2-acetyl-3-cyanoindoIe, which was obtained in 54% yield after recrystallisation. 

Dichloro-phenyl)-ethoxy]-4-methoxy-benzoic acid (0.29 mmol) dissolved in 2 ml DMF was treated with A-ethylmorpholine (1.16 mmol), 1 -pyridin-4-ylmethyl-piperazine (0.29 mmol), and 0-((cyano(ethoxycarbonyl)methylene)amino)-l, 1,3,3-tetramethyluronium tetrafluoroborate (0.3 mmol), then stirred 60 minutes at ambient temperature. The mixture was concentrated, then dissolved in CH2C12, washed three times with saturated NaHC03 solution, dried with Na2S04, and reconcentrated. The residue was purified by chromatography with silica gel using n-heptane/EtOAc, 1 1, then EtOAc, and finally EtOAc/methyl alcohol, 10 1, and 102 mg product isolated. MS ES+, m/z = 500 (M+)... 

The synthesis of 2-aminopyrazines (108) unambiguously substituted at the 5-and 6-positions from substituted 2-azabutadienes (107) and ammonia has been described by Lang and Fleury (488). In this way 2-amino-3-cyano(or methoxy-carbonyl)-5-methyl(or ethoxycarbonyl)-6 phenyl(or methyl or 5,6-polymethylene)-pyrazines have been obtained. When the Schiffbase [H2NC(CN)=C(CN)N=C(CN)Ph ... 

Acetoxylative deoxygenations are as follows. 3-Methoxycarbonylpyrazine 1-oxide refluxed with acetic anhydride for 30 hours gave 2-acetoxy-6-methoxy-carbonylpyrazine (838), but Novdcek et al. (839) claim that the product (prepared with acetic anhydride at 160°) after hydrolysis with water was 2-hydroxy-5( )-methoxycarbonylpyrazine and 2-amino-3-ethoxycarbonylpyrazine 1-oxide refluxed with acetic acid-acetic anhydride gave 3-acetamido-2-ethoxycarbonyl-5-hydroxypyrazine (538). 

Ethoxycarbonyl)-methoxy Tellurium Pentafluoride A well-dried solution of ethyl diazoaeetate in diehloromethane is prepared, eooled in an iee bath, and stirred. A solution of hydroxy tellurium pentafluoride dissolved in diehloromethane is added dropwise until the yellow color of the diazo compound has disappeared and nitrogen is evolved. The solvent is distilled off under atmospheric pressure and the residue is distilled under aspirator vacuum yield 80% b.p. 58"/10 torr. 

Photolysis of l-ethoxycarbonyl-5, 5-dimethyl-3-phenyl-A2-l,2,4-triazo-line (Scheme 32) in benzene in the presence of oxygen and methyl triflu-oroacetate gives the 5-methoxy-2,2-dimethyl-4-phenyl-5-trifluoromethyl-... 

---