Ethyl 2-oxocyclohexanecarboxylate

A mixture of methyl and ethyl 2-oxocyclohexanecarboxylate, available from Aldrich Chemical Company, Inc., may also be used. The product obtained is a mixture of methyl and ethyl 2-methylcyclohexene-l-carboxylates. 

B. Ethyl l-( p-methoxyphenyl I-2-oxoayotohexaneaar hoxylate. A 250 mL, one-necked, round-bottomed flask, equipped with a magnetic stirring bar, is charged with 22.2 g (45 mmol) of p-methoxyphenyl 1 ead triacetate, 10.8 g (135 mmol) of pyridine (Note 8), and 70 mL of chloroform (Note 9). To this solution 1s added 7.0 g (41 mmol) of ethyl 2-oxocyclohexanecarboxylate (Note 10), a calcium chloride drying tube Is put 1n place, and the mixture is stirred at 40°C (Note 11). 

The ethyl 2-oxocyclohexanecarboxylate used was Fluka AG practical grade, and was distilled (bp 106-108 C/12 mm) before use. 

The cyclic /3-keto ester produced in a Dieckmann cyclization can be further alkylated and decarboxylated by a series of reactions analogous to those used in the acetoacetic ester synthesis (Section 22.7). For example, alkylation and subsequent decarboxylation of ethyl 2-oxocyclohexanecarboxylate yields a 2-alkylcvclohexanone. The overall sequence of (1) Dieckmann cyclization, (2) /3-keto ester alkylation, and (3) decarboxylation is a powerful method for preparing 2-substituted cyclohexanones and cyclopentanones. 

Ethyl 2-oxocyclohexanecarboxylate was fluorinated with l-fluoro-2,4,6-trimethylpyridiniuin triflate (1 d) and then treated with sodium hydroxide to give sodium 1 -fluoro-2-oxocyclohexane-carboxylate (21, n = 2 R = Na) in 84% yield.69... 

Cyclocondensation of 2-aminopyridine and its methyl derivatives with ethyl 2-oxocyclohexanecarboxylate in a mixture of polyphosphoric acid and phosphoryl chloride gave 1,2,3,4-tetrahydro-l 1 //-pyrido[2,l -b]-quinazolin-ll-one and its 6-, 7-, 8-, and 9-methyl derivatives (87JMC1543). 

Keto esters also react with salicylaldehyde to yield fused pyrylium salts. For instance ethyl 2-oxocyclohexanecarboxylate affords the tetrahydroxanthylium salt (645), whilst the isochromanone derivative (646) yields the tetracyclic molecule (647), which possesses the skeleton of the anthocyanidin, peltogynidine, isolated from the heartwood of Peltogyne porphyrocardia (Scheme 253) (58JCS3174). 

Substituied-4a-hydroxy-9//-cycloalkvl 1.2-< oxazolo 3,2- ]pyrimidin-9-ones (40) have been prepared by cyclocondensation of 5-substituted-2-amino-2-oxazolines (39) with ethyl 2-oxocyclohexanecarboxylate.64... 

Show the intermediate aldol product in the Robinson annulation reaction of ethyl 2-oxocyclohexanecarboxylate with 1 -penten-3-one. 

Ethyl 2-oxocyclohexanecarboxylate Cyclohexanecarboxylic acid, 2-oxo-, ethyl ester (8,9) (1655-07-8)... 

The three-step sequence of (1) enolate ion formation, (2) alkylation, and (3) hydrolysis/decarboxylation is applicable to all S-keto esters with acidic a hydrogens, not just to acetoacetic ester itself. For example, cyclic fi-keto esters such as ethyl 2-oxocyclohexanecarboxylate can be alkylated and decarboxy-lated to give 2-substituted cyclohexanones. 

Photochemotherapy is an efficient way to treat hyperproliferative diseases. Especially the so-called PUVA therapy (psoralen + UVA light) is very common in which the psoralen is irradiated with UVA light to give rise to a covalent adduct with the pyrimidine bases of DNA by means of a photoaddition reaction. There are several undesired side effects for the patients as a result of this therapy, so the synthesis and photobiological evaluation of novel benzosporalen derivatives was undertaken by the research team of L.D. Via. The key step in their synthetic sequence was the von Pechman reaction of 2-methoxyresorcinol with ethyl 2-oxocyclohexanecarboxylate. 

The radicals obtained by oxidative addition of )S-diketones and jS-keto esters to alkenes undergo oxidative cyclization to give dihydrofurans such as 48 and 49 (Scheme 15) [11a, 34). Enol ethers are more nucleophilic than simple alkenes and therefore react readily with the Mn(IlI) enolates obtained from )ff-diketones and P-keto esters to give 50 and 51 in good yield (Scheme 16) [11a, 35]. a-Substituted j5-diketones and /(-keto esters cannot form dihydrofurans. In these cases the intermediate radical is oxidized and reacts with a nucleophile or loses a proton as in the formation of 52 from isopropenyl acetate and ethyl 2-oxocyclohexanecarboxylate (Scheme 17) [36]. 

Ethyl 2-oxocyclohexanecarboxylate Ethyl chloroformate (7.2 g, 0.066 mole) is added to a well stirred solution of 4-(l-cyclohexenyl)morphoIine (20.0 g, 0.12 mole) in anhydrous benzene (100 ml) under nitrogen, and the mixture is boiled under reflux for 10 h, then cooled and filtered. The precipitate of enamine hydrochloride is washed with anhydrous ether. The united filtrates are treated with 10% aqueous hydrochloric acid (22 ml) and the mixture is stirred vigorously for 15-30 min. The layers are separated, the aqueous phase is extracted with benzene, the organic phases are united, and the solvent is distilled off under reduced pressure. Fractionation of the residue gives 62% (6.2 g) of the /S-oxo ester, b.p. 112-115°/ 10 mm. 

Thus an almost quantitative yield of ethyl l-(hydroxymethyl)-2-oxocyclo-hexanecarboxylate is obtained from ethyl 2-oxocyclohexanecarboxylate and aqueous formaldehyde in the presence of calcium oxide 687 and 2-butanone and formaldehyde in sodium hydroxide solution give a 70% yield of 4-hydroxy-3-methyl-2-butanone, whence 3-methyl-3-buten-2-one is formed in 74% yield by removal of water.688 Hydroxymethylation of acetone689 and of co-nitrotoluene (phenylnitromethane)690 have also been reported. 

In addition, ethyl 2-oxocyclohexanecarboxylate (L19) [27] could promote the copper-catalyzed N-arylation of imidazoles and benzimidazoles under relatively mild reaction conditions (45-75 °C) (entry 6). 

Recently, ethyl 2-oxocyclohexanecarboxylate (L19) [27] also showed good activity for the arylation of amides (entry 7). Interestingly, the reaction even worked at room temperature for some aryl iodides. 

The enol content of ethyl 2-oxocyclohexanecarboxylate is higher than that of the ethyl 2-oxocyclopentanecarboxylate below ([611-10-9]) and varies with polarity of solvent, viz 67% aqueous MeOH (22.2"/o), MeOH (45.1"/o), EtOH (61.7%), CHCI3 (54.5%), C6Hg (74.8%) [Kabachnik et al. Tetrahedron 1 317... 

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