4-Chloroacetoacetate, reaction with

The ammonium formate in formic acid procedure has rendered possible the first preparation of isomeric 4,5-disubstituted oxazoles.03101 Bredereck, Gompper, and Reich101 have reported the anomalous behavior of certain long-chain a-bromo ketones a single a-bromo ketone on reaction with ammonium formate in formic acid gives a mixture of two isomeric oxazoles. Refluxing of a-bromo ketones or of a-chloro-/3-keto esters with ammonium acetate in acetic acid results in the formation of substituted 2-methyl-oxazoles.40 102 Ethyl a-chloroacetoacetate on heating with ammonium carbonate or formamide in formic acid yields 4-methyloxazole-5-carboxylic ester.40 103... 

Mevinphos (96, Phosdrin ) is prepared from methyl 3-chloroacetoacetate in reaction with trimethyl phosphite. Mevinphos (Phosdrin ) is a mixture of Z and E stereoisomers in which the Z isomer was found to be 100 times more active.54 In contrast to mevinphos, E and Z isomers of bromfenvinphos (92) and chlorfenvinphos (94) show no significant difference for a number of biological properties for insecticides.55 The less toxic Clodrin (98) is synthesized from the 1-phenylethoxy ester of 3-chloracetoacetate 97 which is used for control of ectoparasites in horses, cattle, sheep, and swine.54... 

In the presence of sodium hydride in boiling pyridine the anhydride (1) reacts with the alcohols 302 with the formation of anthranilic esters 303 with yields of 41-56%. After diazotization and reaction with a-chloroacetoacetic esters the products are converted into the hydrazonyl chlorides 304 (yields 75-78%). Treatment of the latter with silver carbonate in acetonitrile leads to the tricyclic compounds 305 (yields 14-61%) [189],... 

Miscellaneous Fused Selenophens.—Selenolo[2,3-6]thiophen (691) has been prepared by metalation of thiophen>3-aldehyde diethyl acetal with butyl-lithium followed by reaction with selenium and methyl chloroacetoacetate. The intermediate (692) was, without isolation, hydrolysed and ring-closed to (693), which upon decarboxylation gave (691). Another isomeric... 

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. ... 

Cyclocondensation of 2-amino-6-bromopyridine and 4-chloroacetoace-tate in PPA at 100 °C for 4h afforded a mixture of 2-chloromethyl-, 2-bromomethyl-6-bromo-, and 2-chloromethyl-, 2-bromomethyl-6-chloro-4//-pyrido[l,2-n]pyrimidin-4-ones in 84% yield (99JHC1065). The pyrido-[l, 2-a]pyrimidin-4-ones were separated by preparative reversed phase HPFC. The pure 2-bromomethyl-6-bromo-4//-pyrido[l,2-n]pyrimi-din-4-one was prepared from 2-amino-6-bromopyridine with ethyl 4-bromoacetoacetate in 63% yield. Reaction of 2-aminomethylpyridines and ethyl 4-chloroacetoacetate in PPA at 110°C gave 2-chloromethyl-4//-pyrido[l,2-n]pyrimidin-4-ones (95FFS69, 01H(55)535). 

Because free or esterified imidazole(4,5)-acetates 745 are currently accessible only via a rather tedious multistep synthesis via (4,5)hydroxymethylimidazole [224— 226], it seemed obvious to react amidines such as isobutyraminidine-HCl 742 with commercially available methyl or ethyl 4-chloroacetoacetates 743a, b to obtain 745 directly in one step. Because of the low reactivity of the 4-chlorine in 743, however, reaction of 743, e.g. with isobutyramidine-HCl 742 in the presence of sodium methylate in methanol, affords exclusively 2-isopropyl-6-chloromethyl-pyri-midin-4-one 744 [227], whereas treatment of 743b with NaOEt in EtOH gives, in the absence of amidines, 2,5-bis(ethoxycarbonyl)cyclohexane-l,4-dione in nearly quantitative yield [228, 229]. 

The statin family of pharmaceuticals require a chiral side chain, representing a target that has attracted a great deal of activity focused on preparing various potential intermediates. A number of reports have been published on the reduction of chloroacetoacetate esters for conversion into this target molecule. A method suitable for large-scale production has been published that operates at 36.6gL and 95.2 % yield with 99% ee. This reaction is shown in Figure 1.43. 

The reaction between diethyl phosphite and a-chloroketones can also be accomplished by fluoride ion-mediated deprotonation reaction in DMF (dry KF or KFTHjO as fluoride ion source), which constitutes anonbasic route to diethyl 1,2-epoxyalky Iphosphonates. Unfortunately, the application of this technique provides a mixture of 1,2-epoxyalkyIphosphonate (about 50%) and vinyl phosphate (about 30%) whatever the a-chloroketones. The reaction between 3-(co-bro-moacetyOcoumarin and diethyl or di- -butyl phosphite has been performed with 50% NaOH in CgHg under phase-transfer catalysis conditions with TEBA as catalyst. The only products of the reaction are the epoxyphosphonates isolated in 70% and 34% yields, respectively. In the presence of EtjN, diethyl phosphite reacts with 2-chloroacetoacetate to give diethyl 2-(ethoxycarbonyl)-l-methyl-l,2-epoxyethylphosphonate in 72% yield as a mixture of cis and trans isomers. ... 

A comprehensive study has investigated multidirectional cyclative cleavage transformations leading to bicyclic dihydropyrimidinones [61]. This approach required synthesis of 4-chloroacetoacetate resin as the key starting material this was prepared by microwave-assisted acetoacetylation of commercial available hydroxymethyl polystyrene resin under open-vessel conditions. This resin precursor was subsequently treated with urea and a variety of aldehydes in a Biginelli-type multi-component reaction, leading to the corresponding resin-bound dihydropyrimidinones (Scheme 16.40). The desired furo[3,4-d]pyrimidine-2,5-dione scaffold was obtained by a novel procedure for cyclative release under the action of micro-wave irradiation in sealed vials at 150 °C for 10 min. 

Condensed Selenophens.—The reaction of phenylacetylenesulphonamide with selenium dioxide and hydrogen bromide gave 3-bromo-2-benzo[i>]selenophen-sulphonamide. Heating of (165) with selenium gave (201). " The reaction of 2,3-dimethylselenophen-5-thiol with methyl y-chloroacetoacetate, followed by cyclization with PPA and hydrolysis, gave 4,5-dimethyl-3-selenolo[2,3- >]-... 

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