Tert-Butyl acetoacetate , reaction with

The synthesis of a structurally somewhat more complex indolone tyrosine kinase inhibitor starts with the construction of the pyrrole ring. Reaction of tert-butyl acetoacetate (87) with nitrous acid leads to nitrosa-tion on the activated methylene carbon. This reaction introduces the nitrogen atom that will appear in the target pyrrole. Condensation of 88 with... 

The diazo transfer reaction between p-toluenesulfonyl azide and active methylene compounds is a useful synthetic method for the preparation of a-diazo carbonyl compounds. However, the reaction of di-tert-butyl malonate and p-toluenesulfonyl azide to form di-tert-butyl diazomalonate proceeded to the extent of only 47% after 4 weeks with the usual procedure. The present procedure, which utilizes a two-phase medium and methyltri-n-octylammonium chloride (Aliquat 336) as phase-transfer catalyst, effects this same diazo transfer in 2 hours and has the additional advantage of avoiding the use of anhydrous solvents. This procedure has been employed for the preparation of diazoacetoacetates, diazoacetates, and diazomalonates (Table I). Ethyl and tert-butyl acetoacetate are converted to the corresponding a-diazoacetoacetates with saturated sodium carbonate as the aqueous phase. When aqueous sodium hydroxide is used with the acetoace-tates, the initially formed a-diazoacetoacetates undergo deacylation to the diazoacetates. Methyl esters are not suitable substrates, since they are too easily saponified under these conditions. 

Studies on thebiomimetic synthesis of quinone antibiotics [191] led Krohn to yet another type of enantioselective transformation, namely microbial conversion of an achiral substrate into enantiomericaUy pure anthracych-nones. An adroit synthesis of the microbial transformation substrate, 4-deoxyaklanonic acid (202) [192] (Scheme 38), started from homophthahc ester 196 [193] with addition of diUthiated tert-butyl acetoacetate (197) and subsequent cychzation to isocoumarine 198 [194]. Reaction of 198 with the dilithium salt 199 gave anthrone 200 [195[. Aeration of 200 in the pres-... 

Z)-2-butenylene dicarbonate with dimethyl malonate gives a low yield (20—40%) of 2-vinylcyclopropane-l,l-dicarboxylate with up to 70% ee (Scheme 2-38) [54], Reaction with methyl acetoacetate or acetylacetone takes place in a different manner to give a dihydrofuran derivative (59% ee), which results from nucleophilic attack of enolate oxygen at the cyclization step, (c) Asymmetric elimination of an acetyl-acetate ester gives (R)-4-tert-butyl-l-vinylcyclohexene of up to 44% ee (Scheme 2-39)... 

The 3-(ferf-butyl)-4-hydroxyphenyl motif can likewise be incorporated in extended polyol assemblies. For example, Hostanox 03 ethane-1,2-diyl-bis(3,3-bis(3-(tert-butyl)-4-hydroxyphenyl)butanoate), a product of Clariant, is preferentially used as an antioxidant for plastics with high resistance against hydrolysis. It can be produced on a large scale by the reaction of p-tert-h xXy phenol with methyl acetoacetate in the presence of an alkyl mercaptan and final transesterification with ethylene glycol catalyzed by Bu2SnO (Scheme 2.72) [42]. 

Following the delivery of 4 Kg of ABT-546 for toxicology and clinical studies, we investigated the scope of the novel Michael addition (Table 1). The reaction of ethyl acetoacetate with nitrostyrene proceeded rapidly at ambient temperature to provide the adduct in 90% ee (entry 1). While the bulkier iso-butyl ester also reacted with high selectivity (88%, entry 2), the tert-butyl group proved too bulky and proceeded with significantly lower selectivity... 

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