1,3-Oxazoline-4-carboxylic acid methyl ester

C17H18N2O5S, 5,5-Dimethy1-2-(2-phenoxymethyl-5-0x0-1,3-oxazolin-4-ylidene)-1,3-thiazolidine-4-carboxylic acid methyl ester, 45B, 434 C17H18N2O5S, 6-Methoxyphenoxymethylanhydropenicillin, 39B, 280 Ci7Hi8NftS2, Methylene blue thiocyanate, 39B, 278 C17H1gClN2OS, 7-Hydroxy-2-chloro-10-(3 -dimethylamino-n-propyl)-phenothiazine, 43B, 490... 

Aliphatic carboxylic acids and esters.2 The reagent (1) is converted into an anion which is alkylated at the C2-methyl group (2). The 2-oxazoline ring is then hydrolyzed by heating in 5-7% ethanolic sulfuric acid to give the ethyl ester (3). Reaction of the lithio salt of (1) with an aldehyde, followed by hydrolysis, leads... 

First of all a 2-substituted oxazoline (1) is formed by cyclocondensation of a carboxylic acid ester with 2-aminoethanol and a small amount of (1) is converted with an alkylating agent (e.g., methyl tosylate) to the activated, ionic form (2). 

By judicious choice of chiral auxiliary-reagent pairs, it has been possible to extend this chemistry to the enantioselective synthesis of p-hydroxy-a-methyl-carboxylic acid derivatives having either anti or syn stereochemistry (Schemes 24 and 25). For example, the boron azaenolate obtained upon reaction of (65) with diisopinocamphenylboryl triflate reacts with a series of aldehydes to provide adducts that are readily converted to the anti methyl esters (66) in good overall yields (Scheme 24). The anti.syn ratios for these reactions are typically >9 1, and the percentage enantiomeric excesses for the anti adducts are in the range of 77-85%. On the other hand, the boron azaenolate derived from oxazoline (61c) and 9-borabicyclononane triflate reacts with aldehydes to give adducts that can be converted into the methyl esters of the jyn-carboxylic acids (67 Scheme 25). The symanti ratios in these reactions are typically... 

Another pyrrolidone-based phosphine has been incorporated into amphiphilic, water-soluble diblock co-polymers based on 2-oxazalone derivatives (Scheme 61). The synthesis involved the initial preparation of a diblock co-polymer precursor with ester functionalities in the side chain. This was achieved by sequential polymerization of 2-methyl-2-oxazoline to form the hydrophilic block that provides water solubility, and subsequently a mixture of ester-functionalized oxazoline 147 and 2-nonyl-2-oxazoline, the latter increasing the hydrophobicity of the second polymer block. Having made the backbone, the ester functionalities were converted into carboxylic acids giving polymer 148, which was then reacted with the phosphine ligand to give the desired supported material, 149. This was used in asymmetric hydrogenation reactions with success. 

Oxazolines are formed directly from the reaction of carboxylic acids with 2-ami-no-2-methyl-l-propanol in refluxing toluene but a two-step procedure involving reaction of 2-amino-2-methyl-l-propanol with an acid chloride followed by treatment of the resultant amide with excess thionyl chloride as a dehydrating agent is generally preferred (Scheme 2.128].2 o 26i Alternatives include reaction of dimethylaziridine with a carboxylic acid in the presence of dicyclohexylcarbo-diimide to form the N-acylaziridine followed by acid-catalysed rearrange-ment or reaction of an orthoester, or an imidate ester, with an amino alcohol as illustrated by the conversion of 129.1 to 1293 [Scheme 2.129). ... 

Carboxylic acid 125 was coupled with ethanolamine or L-serine methyl ester hydrochloride in the presence of EDCI, HOBt, and EtsN to afford the corresponding p-hydroxy amides, which were cyclized using bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor) to afford oxazolines (149 and 150, Scheme 24) [56, 57]. Oxazoline 150 was converted to oxazole 151 in 80% yield by treatment with bromotrichloromethane and DBU, conditions which did not lead to epimerization at C-8 [57], A variety of oxadiazoles (152-158) have been produced in 10-56% yield by treating carboxylic acid 125 with appropriate amidoximes in the presence of EDCI and HOBt followed by heating in toluene (Scheme 24) [44, 57, 58]. These conditions led to some epimerization at C-8, necessitating purification by HPLC. Carboxylic acid 125 was treated with either (2-hydroxybenzyl)triphenyl- or (2-thiobenzyl)triphenyl phosphonium bromide in the presence of CDMT and EtsN to afford the benzofuran (159) and benzothiophene (160) products in 26 and 35% yield, respectively (Scheme 24) [58]. 

Methyl esters of carboxylic acids can be used for the formation of oxazolines, but this also requires the heating of reaction mixtures up to 180°C and, hence, seems less convenient in analytical practice. 

Esters of carboxylic acids which are activated by electron-withdrawing groups in the acyl or alkyl portion of the molecule also react with photochemically generated nitrile ylides to produce 5-alkoxy-3-oxazolines in high yield. The addition to the carbonyl group occurs with the same regioselectivity as observed with aldehydes and ketones. Esters which are not sufficiently activated, such as methyl acetate or benzoate, do not undergo cycloaddition. Schmid and coworkers have reported that the ester carbonyl... 

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