Methyl acetoacetate anion

This is a direct SN2 displacement of the bromide anion of ferf-butyl bromoacetate by a methyl acetoacetate anion. Lithium bromide (LiBr), the salt by-product, is not shown in the reaction below. 

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

Schneider and Simon82 prepared / -ketosulfoxides 47a and 47b by sulfinylation of the dianions of the methyl acetoacetates 48a and 48b with sulfinate ester 19 followed by decarboxylation of the intermediate products (Scheme 2). Apparently this avoids racemiz-ation experienced by others in the direct synthesis of these compounds9. /J-Ketosulfoxides are also available from the reaction of the anion derived from methyl p-tolyl sulfoxide with esters (see Section II.E). They can also be obtained, in some cases, through the hydrolysis of a-sulfinylhydrazones whose synthesis is described below. Mention has already been made of the synthesis of 2-p-tolylsulfinylcycloalkanones such as 32. 

The Reissert reaction would now require a base-catalysed acylation of the methyl group with dimethyl oxalate to give 42. They say All attempts. .. in the presence of various bases to produce intermediate [42] failed. So they used the radical bromination of 43 with NBS (chapter 24) to give 51, alkylated with the anion of methyl acetoacetate to give 52. 

In Chapter 24, we introduced the idea that the last-formed anion in a dianion or trianion is the most reactive. Methyl acetoacetate is usually alKylated on the central carbon atom because that is the site of the most stable enolate. But methyl acetoacetate dianion—formed by removing a second proton from the... 

A closely related methodology (route c) involves the dianion from a diketone (R = Me) with the anion of dimethyl malonate (R = Me) (ref.25). The bis-trimethylsilyl ether from methyl acetoacetate has been interacted with the ketalised acid chloride shown (R = CgH ) to furnish the methoxy carbonyl derivative of olivetol (route d) (ref.26). It was also found that pentane-2,4-dione with dimethyl malonate in the presence of sodium hydride afforded methyl orsellinate (ref.26). In a biomimetic approach (route e) a tetraketone has been enzymically cyclised to give the corresponding orsellinic acid (R=H, R = alkyl) (ref. 27). 

Reactions of the nitrile group(s) In general, these reactions start with a nucleophilic attack at the C atom of the nitrile group. Thus 10 reacted with its anion in basic media to yield the dimerization product 2-amino-1,1,3-tricyanopropene . Thiolysis with H2S gave cyanothioacetamide. Acidic alcoholysis in an neutral solvent produced dialkyl propanediimidate dihydrohalides Metal-catalyzed reactions of 10 with methyl acetoacetate and other j5-dicarbonyls have been reported. ... 

Scheme XXXL Synthesis of the 2,7-epimeric analog of perhydrohistrionicotoxin and a 2,7-epi-dioxa analog (75). A i) Methyl acetoacetate dianion, hexamethylphosphoric triamide, ii) Pyrrolidine. B i) 0s04, ii) NaHSOa, iii) Ag2C03, iv) Triethylphosphonoacetate anion. C i)NH3. D i) Toluenesulphonic acid, ii)NaBH4, iii) Phosgene. E i) Al(i-Bu)2H, ii)Allyl-dimethylphenylphosphonium bromide, potassium methylsulfinylmethylide. F i) Pd/C, H2, ii) Li, CH3NH2. G i) LiBH4, ii) KH, C2H5I, iii) Li, CH3NH2...

Alkylation takes place at the most acidic position of a reagent molecule for example, acetoacetic ester (CH3COCH2COOEt) is alkylated at the methylene and not at the methyl group, because the former is more acidic than the latter and hence gives up its proton to the base. However, if 2 mol of base are used, then not only is the most acidic proton removed but also the second most acidic. Alkylation of this doubly charged anion then takes place at the less acidic position (see p. 458). This technique has been used to alkylate many compounds in the second most acidic position. ... 

Another formal total synthesis of ( )-yohimbine has been worked out by Wenkert et al. (229) by preparing O-methylhexadehydroyohimbine (420), which was first prepared by Kametani and co-workers (224-226) as a key intermediate toward ( )-yohimbine. In Wenkert s approach, pyridinium salt 427 was y-alkylated with acetoacetic ester anion. The product 428 then underwent intramolecular condensation, affording tetracyclic quinone 429. Methylation of 429... 

Alkylation of the enolate anion derived from ethyl acetoacetate followed by removal of the ester group is known as the acetoacetic ester synthesis and is an excellent method for the preparation of methyl ketones. The product of an acetoacetic ester synthesis is the same as the product that would be produced by the addition of the same... 

Two very simple precursors combine to produce 2-arylpyrrolo[2,3-6]pyrazines. The anion derived from 2-methylpyrazine (173) adds to a benzonitrile (e.g. (174)) to give the product (175) (Equation (59)). This reaction is not the favored pathway displacement of chlorine is preferred <89TL935> although a similar reaction without the chloro substituent does provide the pyrrolopyrazine as the major product <8iTLi2i9>. However, this reaction does not seem to have been investigated for additional examples. In another simple reaction, 2-aminopyrazine (176) reacts with ethyl chloro-acetoacetate to give ethyl 6-methyl-5//-pyrrolo[2,3-6]pyrazine-7-carboxylate (177) (Equation (60)) <89BSF467>. 

Pass chlorine gas into an ice cold, well-stirred solution of 5 ml acetylketene in 30 ml CCl until there is a 4.5 g increase in weight (solution is slightly yellow). Pour slowly into excess methanol or ethanol at 0° and distill at 118/17 to get 6 ml methyl (or ethyl)-4-Cl-acetoacetate (1). To 2.7 ml methanol saturated with dry HCI at 0°, add a mixture of 10 g (I), 20 g methyl orthoformate (trimethoxy-methane) and 13 g methanol and reflux four hours. Pour hot into 200 ml ice water and adjust pH to 8 with 30% NaOH. Extract four times with ether and evaporate and distill to get methyl (or ethyl)-4-Cl-3,3-dimethoxy-butyrate (II). Dissolve 40 g (11) in 20 ml methanol and add hydroxylamine.HCI in methanol. After ninety-six hours at room temperature (under Nj if possible), evaporate in vacuum. Qan purify the residue by dissolving in water and put on anionic column wash column to neutrality and elute with 2N acetic acid just before the acid elutes, the alkaline fraction giving a positive FeClj test appears evaporate in vacuum this fraction below 40° and dry at 40/0.5 for twelve hours. Dissolve 5 g product in 130 ml glacial acetic acid and saturate at room temperature, then at 0° with dry HCI. Let stand sixteen hours at room temperature and evaporate in vacuum at 40°. Dilute with water and evaporate three times. Extract with 2X130 ml hot ether and filter, evaporate in vacuum to get 3-Cl-methyl-5-OH-isoxazole (111) (recrystallize-acetone). Heat (111) sixteen hours at 90° in concentrated NH OH in autoclave and evaporate to get muscimole. 

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