Ether formation From ester

In the Sepracor synthesis of chiral cetirizine di hydrochloride (4), the linear side-chain as bromide 51 was assembled via rhodium octanoate-mediated ether formation from 2-bromoethanol and ethyl diazoacetate (Scheme 8). Condensation of 4-chlorobenzaldehyde with chiral auxiliary (/f)-f-butyl sulfinamide (52) in the presence of Lewis acid, tetraethoxytitanium led to (/f)-sulfinimine 53. Addition of phenyl magnesium bromide to 53 gave nse to a 91 9 mixture of two diastereomers where the major diasteromer 54 was isolated in greater than 65% yield. Mild hydrolysis conditions were applied to remove the chiral auxiliary by exposing 54 to 2 N HCl in methanol to provide (S)-amine 55. Bisalkylation of (S)-amine 55 with dichlonde 56 was followed by subsequent hydrolysis to remove the tosyl amine protecting group to afford (S)-43. Alkylation of (5)-piperizine 43 with bromide 51 produced (S)-cetirizine ethyl ester, which was then hydrolyzed to deliver (S)-cetirizine dihydrochloride, (5)-4. 

The treatment of an ester (or lactone) with a base and a silyl halide or trillate gives rise to a particular type of sUyl enol ether normally referred to as a silyl ketene acetal. The extent of O- versus C-silylation depends on the structure of the ester and the reaction conditions. The less-bulky methyl or ethyl (or 5-tert-butyl) esters are normally good substrates for O-silylation using LDA as the base. Acyclic esters can give rise to two geometrical isomers of the silyl ketene acetal. Good control of the ratio of these isomers is often possible by careful choice of the conditions. The f-isomer is favoured with LDA in THF, whereas the Z-isomer is formed exclusively by using THF/HMPA (1.24). Methods to effect stereoselective silyl enol ether formation from acyclic ketones are less well documented. ... 

Synthesis of the remaining half of the molecule starts with the formation of the monomethyl ether (9) from orcinol (8). The carbon atom that is to serve as the bridge is introduced as an aldehyde by formylation with zinc cyanide and hydrochloric acid (10). The phenol is then protected as the acetate. Successive oxidation and treatment with thionyl chloride affords the protected acid chloride (11). Acylation of the free phenol group in 7 by means of 11 affords the ester, 12. The ester is then rearranged by an ortho-Fries reaction (catalyzed by either titanium... 

The total syntheses of these pepper alkaloids are not those of pyrrolidines but rather syntheses of their acid parts. Thus dihydrowisanidine (137) has been prepared by a series of reactions, the key step of which is the formation of the carbon-carbon double bond by a Wittig-Homer reaction (217, 218). Schemes 41 and 42 summarize two syntheses of okolasine from sesamolmethyl ether (279) of course, routes to okolasine also yield the corresponding piperidine alkaloid wisanine. Molybdenum-catalyzed elimination of allylic acetate (149) yielded (E,E)-diene ester 150 en route to trichonine (220) worthy of note is the use of an aluminum amide in the preparation of amide 143 from ester 150 (Scheme 43). 

The almost instantaneous intramolecular ether formation by reaction of phenoxy anions, generated from the silyl ethers with a stoichiometric amount of tetra-n-butylammonium fluoride, on mesylate esters has been used to synthesize labile benzo-0-2-isocephams (>90%) [20]. 

Anionicallv Activated Alumina. At this time we had also developed an interest in anionically activated alumina. These basic reagents were active in promoting alkylation(42), condensation(43) and hydrolysis(44) reactions. Thus, we impregnated alumina with sodium hydroxide and used this combination both with and without a phase transfer catalyst (benzyltriethyl ammonium chloride). When BTEAC was added, the conversion to ether was decreased and the formation of ester was noted. In the absence of a phase transfer catalyst, the ether became a minor product and methyl phenylacetate became the major product with coproduction of phenylacetic acid. This ester does not result from esterification of the acid as simple stirring of phenylacetic acid with Na0H/A1203 in methanol does not produce methyl phenylacetate. 

Nothing is yet known concerning the formation of lactvl groups found at 0-9 of sialic acids from different sources, reported in Section II. This is also true of the biosynthesis of methyl ether and sulfuric ester groups occurring in some natural sialic ac ids. 

The physical properties of most acids (esters) and alcohols allow the reaction to be carried out either in the liquid or in the vapour phase. In the liquid phase, the effects of solvents and of transport phenomena may play a more important role than in the vapour phase. On the other hand, the side reactions (mainly the ether and/or olefin formation from the alco- TABLE 20 Reactants and inorganic catalysts used in kinetic studies of esterification (transesterification) ... 

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