Benzyl acetoacetic ester

To a solution of 6 gms. (1 atom) of sodium in 75 c.cs. (excess) of absolute alcohol are gradually added 65 gms. (2 mols.) of acetoacetic ester. 32 gms. benzyl chloride are dropped in, and the temperature of the mixture is maintained at 30° for an hour. It is then refluxed for an hour. The product is distilled under reduced pressure, the fraction 164°—165° at 14 mms. consisting of benzyl acetoacetic ester being retained. Up to this temperature the unattacked acetoacetic ester passes over. 

Hydrocirinamic acid has been prepared by the reduction of cinnamic add with sodium amalgam,1 with hydriodic acid at ioo°,2 and with phosphorus and hydriodic acid 3 by the action of potassium cyanide on /3-phenylethyl chloride followed by hydrolysis 4 by the add hydrolysis of benzyl-acetoacetic ester 5 and by several other methods of no preparative value. It has also been prepared electrolytically by the reduction of cinnamic add in alkaline solution on cathodes of lead 8 and mercury.9... 

Nicardipine Nicardipine, l,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-methyl-2-[(methyl-phenylmethyl)-amino]ethyl ester 3,5-pirididincarboxylic acid (19.3.7), is synthesized in a manner analogous to the synthesis of nifedipine, the only difference being that in the Hantsch synthesis, two different )3-dicarbonyl compounds are used simultaneously with o-nitrobenzaldehyde. During this, one of these in the enamine form of acetoacetic ester is simultaneously used as an amine component. A heterocycUzation reaction is accomplished by reacting, the methyl ester of 8-aminocrotonic acid with the 2-methyl-2-benzyl-aminoethyl ester of acetoacetic acid [24-27]. 

Therefore carry out the acetoacetic ester synthesis using a benzyl halide as the alkylating... 

The synthesis used benzyl acetoacetate 41 for the double alkylation so that the benzyl ester 42 could be specifically cleaved by hydrogenation to give 39. Condensation with unenolisable benzaldehyde is unambiguous (chapter 20) and ozone does the rest. 

FCC) ETHYL ACETYLACETONATE ETHYL BENZYL ACETOACETATE ETHYL-3-OXO-BUTANOATE ETHYL-3-OXOBUTYRATE FEMA No. 2415 3-OXOBUTANOIC ACID ETHYL ESTER... 

Benzyl acetoacetate [5396-89-4] M 192.2, b 130"/2mm, 156-157"/10mm, 162-167"/15mm, 275-277"/atm, d 1.114, n 1.514. Fractionate the ester and collect fractions with the e iected physical properties. Otherwise add ca 10% by weight of benzyl alcohol and heat in an oil bath (160-170°, open vessel) for 30minutes during which time excess of benzyl alcohol will have distilled off, then fractionate. [Bafca-... 

Among procedures for the synthesis of 1,7-naphthyridines, four-component condensation of l-benzyl-3-hydroxy-5-piperidone 101 with 2,3-dichloro-6-fluorobenz-aldehyde, acetoacetic esters and ammonium acetate giving rise to 1,4,5,6,7-hexahydro-l,7-naphtyridin-5-one-3-carboxylic esters 102 attracts attention due to its simplicity. The compounds 102 and their N-debenzylation products 103 exhibit hypotensive activity (1985USP4596873, 1985USP4618678). 

The second classical reaction mentioned above is the acetoacetic ester synthesis. this reaction, an ester of acetoacetic acid (3-oxobutanoic acid) such as ethyl acetoacetate is treated with base under thermodynamic control conditions and alkylated, as with the malonic ester synthesis. Reaction with sodium ethoxide in ethanol (since an ethyl ester is being used) generated the enolate and quenching with benzyl bromide led to 84. Saponification and decarboxylation (as above) gave a substituted ketone (85). Although the malonic ester synthesis and the acetoacetic ester synthesis are fundamentally similar, the different substrates lead to formation of either a highly substituted acid or a ketone. The reaction is not restricted to acetoacetate derivatives, and any p-keto-ester can be used (ethyl 3-oxopentanoate for example). ... 

Carbopalladation of the double bond of the benzyl A/ -vinylcarbamate 124 with benzyl acetoacetate, and subsequent carbonylation affords the amino ester 125, which was converted to a y3-lactam [53],... 

Synonyms Acetoacetic acid ethyl ester Acetoacetic ester Diacetic ether Diacetyl ether EAA EEA Ethyl acetyl acetate Ethyl acelylacetonate Ethyl benzyl acetoacetate Ethyl 3-oxobutanoate Ethyl 3-oxobulyrate 3-Oxobutanoic acid ethyl ester Classification Aliphatic organic compd. 

N-Benzyloxyamino acids have also been esterified (203) to give O-protected substrates (275-277) for the synthesis of N-hydroxypeptides (Scheme 56). To obtain methyl (275), tert-hutyl (276) and benzyl (277) esters diazomethane, tert-huiy acetate with perchloric acid and benzyl chloride with acetoacetate were used, respectively. N-Isopropoxyamino acid esters (291) have also been prepared (203). 

In Scheme 2.25 retrosynthesis is proposed following previous argumentation for TM 2.10. Characteristic reaction conditions are given for the synthetic steps. Since of ethanol is 18 and of the methylenic group in acetoacetic ester is 11, deprotonation of TM 2.10d by sodium ethoxide is completely chemoselective. C-alkylation on the addition of benzyl bromide is followed by acidification and heating to complete the hydrolysis and decarboxylation to TM 2.11. 

The acetone unit is derived from an acetoacetic ester such as ethyl acetoacetate. The alkylating group is available in the form of a halogen derivative such as benzyl chloride. 

Reaction of ethyl acetoacetate with sodium ethoxide followed by addition of benzyl chloride gives an alkylated acetoacetate ester. Subsequent acid-catalyzed hydrolysis with heat leads to decarboxylation of the P keto acid. 

This group can be installed via an acetoacetic ester synthesis, using benzyl bromide. 

An acetoacetic ester synthesis begins with the deprotonation of ethyl acetoacetate (using ethoxide as a base). The resulting resonance-stabilized conjugate base is then treated with benzyl bromide, thereby installing a benzyl group. Subsequent hydrolysis and decarboxylation give the product, as shown ... 

Ethyl Acetoacetate. -The e. planation of the manner in which this substance is produced has been given in the account of the preparation. The result was anived at, not by the iscila-tion of the intermediate compound formed by the union of ethyl acetate with sodium ethylate, but by analogy with the behaviour of benzoic methyl ester with sodium benzylate, which gave the same additive product as that obtained by combining benzoic benzyl ester with sodium methylate, showing that such combinations could occur,... 

Acetoacetic acid N-benzyl-N-methyiaminoethyl ester -Aminocrotonic acid methyl ester m-Nitrobenzaldehyde... 

A mixture of 4.98 g of acetoacetic acid N-benzyl-N-methylaminoethyl ester, 2.3 g of aminocrotonic acid methyl ester, and 3 g of m-nitrobenzaldehyde was stirred for 6 hours at 100°C in an oil bath. The reaction mixture was subjected to a silica gel column chromatography (diameter 4 cm and height 25 cm) and then eluted with a 20 1 mixture of chloroform and acetone. The effluent containing the subject product was concentrated and checked by thin layer chromatography. The powdery product thus obtained was dissolved in acetone and after adjusting the solution with an ethanol solution saturated with hydrogen chloride to pH 1 -2, the solution was concentrated to provide 2 g of 2,6-dimethyl-4-(3 -nitrophenyl)-1,4-dihydropyridlne-3,5-dicarboxylic acid 3-methylester-5- -(N-benzyl-N-methylamino)ethyl ester hydrochloride. The product thus obtained was then crystallized from an acetone mixture, melting point 136°Cto 140°C (decomposed). 

Acetoacetic acid N-benzyl-N-methyl-amino ethyl ester Nicardipine... 

Another example illustrates the utility of ethyl acetoacetate in the synthesis of chrom-2-enes. Reaction of the /3-keto ester with the benzyl halide (173) affords the hydroxyphenylpropanone (174) which forms the chromene with acetic anhydride (Scheme 27) (42JA435). 

Substituted a-benzylacetoacetic esters have usually been prepared by the general method of Leuchs,4 in which ethyl aceto-acetate is alkylated in ethanol solution with benzyl chloride and sodium ethoxide. The present method is based upon Cope s 6 procedure for the condensation of carbonyl compounds with ethyl acetoacetate, followed by catalytic reduction of the condensation product. 

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