3- Methylbut-2-enoic acid chloride

The 8-oxo-7-phenylacetylamino-5-thia-l-aza-bicyclo[4.2.0]oct-l-ene-2-carboxylic acid benzhydryl ester is reacted with phosphorus pentachloride/pyridine reagent in methylene dichloride, and the reaction mixture is thereafter cooled to -35°C and treated with methanol to produce hydrochloride of 7-amino-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester. This hydrochloride is reacted with 4-(3-aminothiophen-2-yl)-5-oxohex-3-enoic acid 3-methylbut-2-enyl ester. Then 7-[2-(2-benzoylamino-thiazol-5-yl)(3-tert-butyl-4,4-dimethylpent-2-enoxycarbonyl)-pent-2-enoylamino]-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid synthesized is reacted with aluminum chloride in anisole and diluted hydrochloric acid and then with dimethylmalonate to give 5-thia-l-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, 7-(((2Z)-2-(2-amino-4-thiazolyl)-4-carboxy-l-oxo-2-butenyl)amino)-8-oxo-, (6R,7R)- (Ceftibuten). 

By contrast, reaction of phloroglucinol with 3,3-dimethylacrylic acid (3-methylbut-2-enoic acid) in the presence of anhydrous aluminium chloride and phosphorus oxychloride by agitation during 5 hours at ambient temperature gave a 90% yield of 2,2-dimethyl-5,7-dihydroxychroman-4-one (ref.9). 

The Cs-phosphonium ester salts 95 + 99 and the Cs-phosphonate ester 100 (Scheme 11), as well as their corresponding methyl esters, are key building blocks for the manufacture of various polyenecarboxylic acid esters for use in the carotenoid field [34-36]. An efficient route uses as an intermediate 2-hydroxy-2-methylbut-3-enoic acid ethyl ester (101) [37,38], which can be prepared from methylvinyl ketone (102) by acidic ethanolysis of the cyanohydrin 103, prepared by reaction of 102 with HCN (104). Reaction of 101 with thionyl chloride under reflux conditions led to a 76% yield of distilled 4-chloro-2-methyl-but-2-enoic acid ethyl ester (105), from which the phosphonium chloride 98 was obtained in good yield [36]. 

Recently, a novel process has been developed [40] for the manufacture of the phosphonium chloride 98 and the corresponding ethyl sulphate 110. The process comprises a-chlorination of 2-methylbut-3-enenitrile (106) by means of an alkali-metal hypochlorite, after which the 2-chloro-2-methylbut-3-enenitrile (111) formed is subjected either first to an ethanolysis to give the corresponding 2-chloro-2-methylbut-3-enoic acid ethyl ester (112) and then reaction of 112 with triphenylphosphine to give the desired phosphonium chloride 98, or first the reaction of 111 with triphenylphosphine to obtain (3-cyanobut-2-enyl)triphenyl-phosphonium chloride (113) and then the ethanolysis of 113 with concentrated sulphuric acid to give the corresponding ethyl sulphate 110. 

Draw (a) 2,3-diphenylhex-2Z-enoic acid, (b) 3-methylbut-2-enoyl chloride, and (c) methyl 4-phenylbut-2E-enoate. 

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