Monoethyl malonate

It is now applied more widely to include malonic acid derivatives, such as diethyl monoethyl-malonate, ethyl cyanacetate, etc. Various amines may be used as catalysts, and usually the most effective is piperidine (hexahydro-pyridine) a mixture of piperidine and pyridine, or pyridine alone, is also often used. 

Similarly, the dilithium dianion of monoethyl malonate is easily alkylated and the product decarboxylates after acidification.50... 

Methyl monoethyl malonate and 2-methylacetoacetic acid, however, did not give definite condensation products. 

N-Methyb/>-toluenesulfonamide, 34, 97 /3-Methyl-S-valerolactone, 35, 87 Methyl vinyl ether, 34, 29 Methyl vinyl ketone, 37, 19 Michael condensation between 3-nitropro-pane and methyl acrylate, 32, 86 Monochlorourea, 30, 24, 25, 26 Monoethanolamine, 32, 19 Monoethyl malonate, 37, 34 Mucobromic acid, 32, 95... 

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 monoethyl A -(6-methyl-2-pyridyl)aminomethylenemalonate was prepared in 34% yield in the reaction of monoethyl malonate, ethyl orthoformate, and 2-amino-6-methylpyridine in the presence of catalytic amounts of A1C13 at 110-115°C for 45 min (72AF815). 

The 2,2 -bisindole (1384), required for the synthesis of staurosporinone (293) and the protected aglycon 1381, was prepared by a double Madelung cyclization as reported by Bergman. For the synthesis of the diazolactams 1382 and 1383, the glycine esters 1385 and 1386 were transformed to the lactams 1389 and 1390 by DCC/DMAP-promoted coupling with monoethyl malonate, followed by Dieckmann cyclization. The lactams 1389 and 1390 were heated in wet acetonitrile, and then treated with mesyl azide (MsNs) and triethylamine, to afford the diazolactams 1382 and 1383. This one-pot process involves decarboethoxylation and a diazo transfer reaction (Scheme 5.234). 

Monoethyl malonate Malonic acid, monoethyl ester (8) Propanedioic acid, monoethyl ester (9) (1071-46-1)... 

ALIPHATIC AND AROMATIC P-KETOESTERS FROM MONOETHYL MALONATE ETHYL 2-BUTYRYLACETATE... 

Ethyl 2-butyrylacetate. In a 1-L, three-necked, round-bottomed flask fitted with a mechanical stirrer, dry nitrogen inlet, and thermometer is placed 19.8 g (0.150 mol) of monoethyl malonate (Note 1), 350 mL of dry tetrahydrofuran (THF, Note 2), and 5 mg of 2,2 -bipyridyl. The solution is cooled to approximately -70°C (in an isopropyl alcohol-dry ice bath) and a 1.6M solution of n-butyllithium in hexane is added from a dropping funnel while the temperature is allowed to rise to approximately — 10°C. Sufficient n-butyllithium is added (approx. 190 mL) until a pink color persists for several minutes (Note 3). The heterogeneous solution is recooled to -65°C and 7.90 mL (7.98 g, 75 mmol) of iso-butyryl chloride (Note 4) is added dropwise over 5 min. The reaction solution is stirred for another 5 min (Note 5) and then poured into a separatory funnel containing 500 mL of ether and 300 mL of cold, 1 N hydrochloric acid (Note 6). The funnel is shaken, the layers are separated, and the organic phase is washed with two 150-mL portions of saturated aqueous sodium bicarbonate, followed by 150 mL of water, and dried over anhydrous sodium sulfate. Removal of the solvents under reduced pressure leaves 11.70 g (98%) of ethyl 2-butyrylacetate (Note 7). The crude product can be distilled at 70-74°C (7 mm) (80% yield, 96% purity by GLC). 

The potassium salt of monoethyl malonate, available from the Aid-rich Chemical Company, Inc., can be used after neutralization. Direct... 

The optimum ratio for high yields of fS-ketoester is 1.7 (monoethyl malonate acid chloride). A nonstoichiometric reaction for optimum yield is not a serious drawback in this case since the reagent in excess is the inexpensive dilithio monoethyl malonate. Our results show that lowering the ratio also lowers the yield, whereas an increase in the ratio beyond 1.7 has little effect. 

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