Bromoacetic esters

The regioselecdve cross-coupling between anions of bromomalonate esters or bromoacetate esters and m-dirutrobenzene proceeds in the presence of copper tfirr-bntoxide to give the 3-snbsdtiited product Without the copper salt, the4-snbsritiited isomer is the only product fEq 9 35,... 

A terpene yielding isofenchyl alcohol on hydration, which Wallach considers to be one of the fenchenes, was artificially prepared by converting nopinone into a hydroxy ester by means of bromoacetic ester and zinc-dust. The hydroxy ester is dehydrated by potassium bisulphate, and so yields an unsaturated ester, which on saponification yields an acid from which the terpene results by distillation. This fenchene has the following characters —... 

Alkylation of trifluoro- and trichloroacetamides with a-bromoacetic esters has been utilized for the synthesis of a wide range of a-aminoacetic acids [11-13] (Table 5.13). Hydrolysis of the intermediate a-trihaloacetamidoacetic esters with methanolic potassium hydroxide converts the methyl and ethyl esters directly into the amino carboxylic acids. /-Butyl a-aminoacetates are more stable, but they are hydrolysed under phase-transfer catalytic conditions (see Chapter 9.2). Reaction of the trihaloacetamides with 1,4-dibromobutane and 1,5-dibromopentane and subsequent hydrolysis provides a simple route to pyrrolidine-2-carboxylic acid (75%) and piperidine-2-carboxylic acid (58%) [11, 12],... 

Anhydrous K,C03 (5.53 g, 40 mmol) is added to the trihaloacetamide (40 mmol), TEBA-C1 (0.46 g, 2 mmol) and the a-bromoacetic ester (20 mmol) in MeCN (40 ml) at room temperature. The mixture is stirred under reflux until the reaction is complete, as shown by TLC analysis. The mixture is cooled, filtered through Celite, and evaporated to yield the crude a-trihaloacetamidoacetate, which is purified by chromatography. 

By treatment with sodium telluride, bromoacetic esters react with aromatic and non-eno-lizable aldehydes in aprotic solvents, giving a, -unsaturated esters. - ... 

Reformatsky reaction -b-hydroxy acids [HYDROXYCARBOXYLIC ACIDS] (Vol 13) -use of bromoacetic esters [ACETIC ACID AND DERIVATIVES - HALOGENATED DERIVATIVES] (Vol 1)... 

An enantioselective one-pot, three-component imino-Reformatsky reaction has been reported.20 Combining a benzaldehyde, an aniline, and an alkyl bromoacetate ester, (g) ees of up to 92% have been achieved in the /i-amino ester product, using a recyclable A-methylcphedrinc as auxiliary. A nickel(II) salt and dimethylzinc are employed the latter serves as dehydrating agent, reductant, and coordinating metal. 

It was felt that a similar alkylation reaction would allow the facile introduction of the kainoid C-3 side chain if a bromoacetate ester was used in place of allyl bromide as the alkylating agent. The aim was to attempt to increase stereoselectivity by using the bulky ester tert-butyl bromoacetate. Appropriately protected 4-keto-L-proline 39 derivatives... 

If the reaction between the enol and the electrophile proceeds extremely fast, the enol tautomer of a carbonyl or carboxyl compound might be consumed completely. The generation of enol becomes the rate-determining step. This situation occurs with the enol titration of ace-toacetic ester, (Figure 12.4). In this process, bromine is added to an equilibrium mixture of the ketone form (B) and the enol form (iso-B) of an acetoacetic ester. Bromine functionalizes the enol form via the intermediacy of the carboxonium ion E to form the bromoacetic ester D. The trick of conducting the enol titration is to capture the enol portion of a known amount of acetoacetic ester by adding exactly the equivalent amount of bromine. From the values for... 

The promising analgesic activity of 3-hydroxy-17-methylmorphinan stimulated Schnider and Hellerbach(11,12) to seek a commercial synthesis of it via 8. Bromoacetic ester reacted with cyclohexanone to give 10, which was converted rather laboriously to 8 (Scheme 3.2), Cyanoacetic ester afforded a more fluent route by way of cyclohexenylacetonitrile (11). In the presence of... 

Chase and Tubbs (1969) prepared the bromoacetate ester of carnitine by taking the appropriate enantiomer of carnitine chloride, dissolving it in bromoacetic acid at 53°C and heating it with an excess of bromoacetyl bromide for 4 hr. Excess bromoacetic acid and bromoacetyl bromide was removed by distillation in vacuo. The residue was dissolved in absolute ethanol and precipitated by ether. The derivatives can be recrystallized from butanol. 

As a synthetic route, this organoborane synthesis parallels the aoetoaoetic ester and malonic ester syntheses. An acetone unit is furnished by acetoacetic ester or, here, by bromoacetone an acetic add unit is furnished by malonic ester or, here, by bromoacetic ester. In these syntheses, bromine plays the same part that the —COOEt group did by increasing the acidity of certain a-hydrogens, it determines where in the molecule reaction will take place it is easily lost from the molecule when its job is done. Unlike the loss of —COOEt, the departure of —Br is an integral part of the alkylation process. 

Eliminations. Specially designed sulfones undergo elimination which is initiated by a remote radical. The alkyl moiety is converted to an alkene. The core of the squalene synthase inhibitor CP-225917 has been synthesized via a radical cyclization with ejection of an allylic phenylthio group. The radical precursor is an a-bromoacetic ester. 

Conjugate addition. Formation of Y,y-dicyanobutanoic esters from alkylidenemalononitriles and bromoacetic esters is effected by Cp TiCl -Zn (13 examples, 43-93%). 

Thiophene derivatives were also afforded in water by Dong and Liu. The polysubstituted thiophene and polysubstituted thieno[2,3-b]thiophenes have been obtained in high yields. The reaction of 1,3-dicarbonyl compounds and bromoacetic ester was catalyzed by aqueous tetrabutylammonium bromide (TBAB) in the presence of CS2 and K2CO3 (Scheme 5.21). After isolation of product the aqueous solution of TBAB was recycled for subsequent reactions. 

Two convenient approaches to (diphenylphosphono)acetic esters (258) have been reported. One approach involves the reaction of chloroformate esters with the carbanion of diphenyl methylphosphonate and the other a Michaelis-Becker reaction of bromoacetic esters (Scheme 41) the former reaction gives better yields than the latter. Olefination reactions of (258) with benzaldehyde and... 

We have found it more convenient to prepare (carbethoxymethyl)-triphenylphosphonium bromide in situ in the same reaction vessel from triphenylphosphine and ethyl bromoacetate. This effectively provides a one-pot preparation for the a-acylmethylenephosphorane from triphenylphosphine and allows facile incorporation of various esters, by employing different bromoacetate esters, in the acetylenic product. The yield and purity of the resultant phosphorane is unaffected by the following one-pot procedure. 

Metabolite C was first recognised by metabolic studies using [2- C]abscisic acid synthesised in the normal way from [2- C]bromoacetic ester. t-Butyl chromate oxidation of a-ionone provides an efficient synthesis of abscisic acid (Scheme 3). A large number of compounds related to abscisic acid have been synthesised to check their biological activity. In general, conventional synthetic methods were used. The Reformatsky reaction may be used as an alternative to the Wittig reaction for the synthesis of a-ionylidene acetic ester. 

Diazoacetic esters. Diazoacetic esters are prepared from reaction of bromoacetic esters and TsNHNHTs and DBU (base) in THF at 0°. 

The halogen acid can be bound by a second molecule of ylide, as above. R may be an alkyl, allyl, or arylalkyl group, but a-bromo ketones, bromoacetic esters, and chloroacetonitrile have also becen used.456,462... 

Z)-a,P-Unsaturated esters. The condensation with aldehydes (Emmons-Wadsworth reaction) using these esters is stereoselective. Two convenient preparative methods for the reagents are (1) reaction of (PhO)2P(0)H with bromoacetic esters in dichloromethane, (2) alkoxycarbonylation of (PhO)2P(0)Me with CICOOR. In the latter protoeol, because anions of the methylphosphonate are very unstable, the acylating agents must be present before addition of base to (PhO)2P(0)Me. 

The alkylation of / -sultams has been achieved using the phase transfer method developed for /Mactams (equation 220)274 Activated alkyl halides such as alkyl bromides and benzyl bromide react very rapidly, a-bromoacetic esters less so and secondary alkyl halides hardly at all242. Although acylation of / -sultams in the 2-position causes... 

Unsaturated esters. Alkylation of the corresponding ylides with a bromoacetic ester generates conjugated esters directly. 

A modification of the Westphal synthesis is based on 2-substituted pyridines 18. They are obtained by (9-acylation of the aldol adducts 17 obtained from pyridine-2-carbaldehyde and methylene ketones. The pyridines 18 are quatemized with bromoacetic ester or bromoacetonitrile to 19, followed by base-catalysed cyclization giving 2,3,4-trisubstituted quinolizinium ions 20 ... 

Debromination and decyanation. A selective synthesis of 6a-bromopenicillinates is accomplished by partial reduction of the 6,6-dibromo compounds (7 examples, 88-100%). a-Bromoacetic esters undergo reductive coupling to give succinic esters."... 

The epimeric mixture of 16-ethoxycarbonylmethyl-17-oxo-compounds (45) was prepared from the jS-keto-thiolesters (44) by successive alkylation with bromoacetic ester and treatment with Raney nickel. The epimeric 16-phenyl-selenylandrostenones (46) were prepared via LDA-PhSeCl reaction of the 17-oxo-compound appropriately protected at C-3. Similar reaction of a 20-oxopregnane gave the 21-phenylselenyl derivative (47), and the preparation of the 17a-phenylselenyl analogue involved the reaction of the A -enol acetate... 

Thiazolidines incorporating a hydroxyamine function (258) are formed directly by the condensation of iV-hydroxythioureas (257) and chloroacetyl chloride. They are isomerized to the 3-aryl-2-hydroxyiminothiazolidin-4-ones (259) by methanolic sodium methoxide. 2,3-Disubstituted thiazolidin-4-ones of type (261) are accessible by the condensation of the appropriate thioamides (260) with bromoacetic ester. l-Acyl-1,3,3-trichloroprop-2-enes (263), showing the usual reactivity of a-chloroketones, react with thiourea to yield 4-substituted 2-amino-5-(2, 2 -dichlorovinyl)-4-hydroxythiazolidines (262). The pyrimidine derivative (264), bearing three thiazolidine nuclei, is formed from trithiobarbituric acid by an application of this synthesis. ... 

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