Ethyl 4-chloroacetoacetate

The only tetrasubstituted furans that have been prepared using the Feist-Benary reaction are substituted tetrahydrobenzofurans and octahydrodibenzofurans. This strategy was pioneered by Stetter and Chatterjea and applied in a series of total syntheses by Magnus. Stetter demonstrated that 1,3-cyclohexanedione (30) can act as the P-dicarbonyl component and readily combines with either 3-bromo-2-ketobutyric (29) acid or ethyl 2-chloroacetoacetate (32) in the presence of potassium hydroxide to yield tetrahydrobenzofuran derivatives 31 and 33, respectively. ... 

Magnus prepared tetrahydrobenzofuran 37 using a Feist-Benary reaction of ethyl 2-chloroacetoacetate (32) and functionalized 1,3-cyclohexanedione 36. Compound 37 was a key synthetic intermediate in Magnus s synthesis of linderalactone, isolinderalactone, and niolinderalactone. ... 

The same substrate (25) aud ethyl 2-chloroacetoacetate gave an analogous product, ethyl 3-hydroxy-3-methyl-3,4-dihydro-2//-1,4-thiazino[2,3-h]qui-noxahne-2-carboxylate (27) (KOH, EtOH, 20°C, 3 h 58%), which underwent dehydration to ethyl 3-methyl-2H-1,4-thiazino[2,3-h]quinoxaline-2-carboxy-late (28) (HCl gas, EtOH, 20°C, 15 h 60% analogs likewise). ... 

Cas/liquid reaction 4 [CL 4] Fluorination of ethyl 2-chloro-3-oxobutanoate (ethyl 2-chloroacetoacetate) [15, 16]... 

GL 4] [R 5] [P 5] The rate of the fluorination of y0-keto esters is usually correlated with the enol concentration or the rate of enol formation as this species is actually fluorinated [15, 16]. For the fluorination of ethyl 2-chloroacetoacetate in a micro reactor, much higher yields were found as expected from such relationships and as compared with conventional batch processing which has only low conversion. Obviously, the fluorinated metal surface of the micro channel promotes the enol formation. 

Treatment of the ethanolamine derivative 298 with PPA results in a mixture of two isomeric imidazotriazolopyrimidines 299 and 300 <2002JHC319> (Equation 51), and treatment of triazoloquinazoline 301 with ethyl 2-chloroacetoacetate in ethanol gives the imidazotriazoloquinazoline 302 <2003AP560> (Equation 52). 

Bohme and Weisel obtained 4-oxo-4//-pyrid o [ 1,2-a] pyrimidine (59) from 2-aminopyridine and ethyl 2-chloroacetoacetate. The yield was 10% in toluene in the presence of p-toluenesulfonic acid, 30% in acetic acid, and 59% in polyphosphoric acid. The triethylamine-catalyzed reaction in benzene led to the imidazo[l,2-a]pyridine 58.64 4-Oxo-4//-pyrido[ 1,2-a]-pyrimidine (59) was also prepared from 2-aminopyridine and 2-chloro-3-oxobutyronitrile.67... 

Ethyl (8//)-pyrimido[5,4-fc][l,4]oxazine-6-carboxylate (187) could be obtained in about 82% yield by boiling 6-amino-4-chloro-5-hydroxypyrimidine (186) with ethyl 2-chloroacetoacetate in ethanol, i.e. triethylamine <73KGS1694>. 

Aryl-4-formylsydnone 4 -phenylthiosemicarbazones 183 were treated with ethyl 2-chloroacetoacetate and 2-bromoacetophenone in buffer systems of sodium acetate and acetic acid, to produce anti-oxidants 2-[(3-arylsyd-non-4-ylmethylene)-hydrazono]-4-methyl-3-phenyl-2,3-dihydrothiazole-5-carboxylic acid ethyl esters 184 and 3,4-diphenyl-2-[(3-arylsydnon-4-ylmethylene)hydrazono]-2,3-dihydrothiazoles 185 in good yields (Scheme 71) <2004BMC4633>. 

Several tetrasubstituted furan derivatives have been prepared by the Feist-Benary reaction. For example, Stetter and Lauterbach demonstrated that 1,3-cyclohexanedione could serve as a P-dicarbonyl in combination with ethyl 2-chloroacetoacetate in the presence of potassium hydroxide to yield the corresponding fused tetrasubstituted furan derivative in good yield. ... 

Magnus and co-workers extended on work by Stetter and Lauterbachr to produce an intermediate common to the natural products linderalactone, isolinderalactone and neolinderalactone. Compounds of this class have been shown to exhibit a host of biological properties including analgesic, anti-inflammatory, antiemetic, antibacterial and antiviral. The Feist-Benary reaction of ethyl 2-chloroacetoacetate and 5-(methoxymethyl)-5-methylcyclohexane-l,3-dione in the presence of potassium hydroxide gave the desired tetrasubstituted furan in 57% yield. 

Keywords Ammonium thiocyanate, benzoyl chlorides, ethyl bromopyruvate, ethyl 2-chloroacetoacetate, A-methylimidazole, solvent-free, room temperature, one-pot multicomponent reaction, condensation, l,3-oxazoline-2-thiones... 

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