Bis-ester

To a solution of the ester amide (160 mg, 0.26 mmol) in methanol (3 mL) and THF (3 mL) was added a 1 M solution of NaOMe in methanol (5 mL). The mixture was stirred at rt for 1.5 d then neutralized with methanolic acetic acid and concentrated in vacuo. The crude material was partitioned between water and CH2CI2. The organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to afford the bis(ester) 73 as a colorless solid, mp 154.4-155.5 C, [a] -17° (c = 0.3, MeOH). 

A Michaelis-Arbusov rearrangement followed by a Wittig-Horner reaction is involved in preparation of the distyrylbenzene derivative 11.37, as shown in Scheme 11.15. Precautions must be taken in the first stage to minimise formation of the carcinogenic by-product bis(chloromethyl) ether 11.16. The stilbene bis-ester 11.38 can be made by a similar procedure, or alternatively by the reaction of ethyl acrylate with 4,4 -dibromostilbene in the presence of a palladium-based catalyst (Scheme 11.16), a synthesis that yields the required trans form of the brightener. 

Subsequently, it was shown that if the gorgonian is handled with extreme care (frozen with liquid N2 at the time of collection and then extracted with organic solvents) only the bis-ester of PGA2 (36) is isolable [64], If the coral is allowed to stand in water or methanol at room temperatures before extraction, a mixture of methyl 15R-acetoxy-PGA2 (36), methyl 15K-PGA2 (37), and 15/ -PGA2 (34) is obtained. These findings help to explain the wide array of acetate (35) and methyl esters that have been isolated in the many studies of Plexaura chemistry. 

Another application is the esterification of menahydroquinone-4, a water-insoluble vitamin K, with V,A-dimethylglycine [144], The 1-mono, 4-mono, and 1,4-bis esters were found to be water-soluble and rapidly hydrolyzable by liver and plasma esterases. A rapid pharmacodynamic response was seen after intravenous administration of the prodrugs. 

A double aza-Michael addition was enforced by high pressure in the reaction of primary amines with the ,/l-unsaluraled bis ester (92) to afford the azanorbomyl derivatives (93).141... 

Figure 12.9 Regioselectivity of the hydrolysis of hydroquinone bis-esters (Rubio, 1991).

The decision in In re Albrecht results from an appeal from the USPTO to the CCPA where the applicants eight claims directed to bis-esters and bis-amides of carbazoles were rejected.25 Claim 1 of the invention, directed to a Markush genus of compounds is reproduced in its entirety from the opinion and shown in Figure 8.1. 

The above bis ester (2.5 g) was refluxed with sodium bicarbonate (1.64 g) in ethanol (100 ml) and water (50 ml) for 1.5 hours. The whole was poured into water and acidified to precipitate a gelatinous solid. This was collected by filtration, refluxed with ethanol and the product was separated by centrifugation (1.4 g), mp 303°-304°C dec. The structure of the product was confirmed by mass and NMR evidence. 

Another example of the nucleophilic chloro ligand substitution involves the reaction of the zirconium dichloride complex 468 with lithium ester enolates (Scheme 112). Its reaction with 2 equiv. of stable lithium ester enolates such as lithium tert-butyl isobutyrate in TF1F produces the bis(ester enolate) complex 499 as a crystalline solid.344 The same reaction but with the unstable lithium methyl isobutyrate leads to the isolation of the decomposition product, the bis(methoxide) complex 500, which exists as a dimer in the solid state. Treatment of the bis(ester enolate)... 

Reagents. Hydroxyethyl methacrylate (HEMA) was extracted with hexane to remove bis-esters and distilled in vacuo, b.p. 69 / 0.1 mm Hg. p-Mltrobenzenesulfonyl isocyanate (b.p. 160 /A mm Hg) was synthesized in 63% yield by phosgenatlon of p-nltrobenzene-sulfonamlde in the presence of butyl isocyanate (9 ). Homo- and copolymers of HEMA were prepared by solution polymerization in DMF in the presence of benzoyl peroxide and the results are summarized in Table I. The hydrolytic stability of the hydrogels was estimated by slurrying 0.5-1.0 g of polymer in 5.0 mL 0.35 KOH in 10 mL culture tubes equipped with teflon lined screw caps. The samples were heated at 100 for up to 24 hr in an aluminum constant temperature block. Immediately upon removal from the heating block, the samples were cooled and acidified with 6N HCl. The precipitated gel was washed and soaked in distilled water for 30 min before the carboxylic acid content was estimated by titration with standard NaOH. 

In analogy to the n = 2 template 14, template 24 was prepared according to Scheme 8-8. This compound was prone to light initiated polymerization when left concentrated and therefore was stored as a stock solution typically on the order of 1.0 M in benzene. The n = 4 base was synthesized starting from protocatechuic acid. Bis-ester formation was... 

The use of bis-ester tethers in remote intramolecular glycosylation has been investigated by a number of groups. In contrast to the short tethers used by Stork, Hindsgaul, and Ogawa, these more remote tethers provide a much less predictable outcome and as a result they remain less synthetically useful. Another difference between the short tethers and remote bis-ester tethers is that the reacting alcohol functionality is not masked in the tether but is already free to react as soon as the anomeric center is activated. 

By changing the anchoring sites of the bis-ester template, it is possible to reverse completely the regioselectivity of the coupling [97 b]. For example, when a phthalyl tether was used to link the 2-OH of a glucosyl acceptor to the 6-OH of a mannosyl donor to... 

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