Benzyl ester group

I) Refluxing said benzyl ester with an aqueous alcoholic alkali metal hydroxide solution to saponify the benzyl ester group, neutralizing the saponification mixture by the addition of hydrochloric acid, extracting the neutralized mixture with chloroform, and separating the resulting (S,N-ditrityl-L-cysteinyl)-L-proline. 

Intermediate 10 must now be molded into a form suitable for coupling with the anion derived from dithiane 9. To this end, a che-moselective reduction of the benzyl ester grouping in 10 with excess sodium borohydride in methanol takes place smoothly and provides primary alcohol 14. Treatment of 14 with methanesulfonyl chloride and triethylamine affords a primary mesylate which is subsequently converted into iodide 15 with sodium iodide in acetone. Exposure of 15 to tert-butyldimethylsilyl chloride and triethylamine accomplishes protection of the /Mactam nitrogen and leads to the formation of 8. Starting from L-aspartic acid (12), the overall yield of 8 is approximately 50%, and it is noteworthy that this reaction sequence can be performed on a molar scale. 

The benzyl ester group was selectively hydrogenolyzed on 10% Pd/C in EtOH-H20 (9 1) at 15 psi H2 for 15 hours without concomitant removal of the imidazoyl benzyl moiety (Scheme 4.88).337... 

The Pyoc group is stable to acids and bases, but may be selectively removed after conversion into the jV-methylpyridinium form and subsequent treatment with morpholine, to give 146. Treatment of 146 with acetic anhydride in pyridine gave 147. Hydrogenolysis of the benzyl ester group of 147 followed by methanolysis catalyzed by hydrazine afforded (44,73) the de-protected derivative 148. 

The /-butyl ester is often prepared by acid-catalyzed addition of the carboxylic acid to isobutylene. The overall protection-deprotection sequence is outlined in the following equation. Note that the /-butyl group is removed in the last step without destroying the phosphorus ester or the amide or benzyl ester groups. 

An interesting modification of the benzyl ester group is the introduction of chromo-phores that allow visual monitoring of the isolation and purification steps. Esters of 4-(dimethylamino)-4 -(hydroxymethyl)azobenzene additionally provide a basic substituent that enables attachment to ion-exchange resins and thus facilitates removal of excess starting materials, e.g. acylating agents, and possible byproducts.P ... 

Now see what happens if we replace the achiral benzyl ester group with an amide derived from the natural amino acid valine (Chapter 49). The diastereoselectivity remains the same but the chiral environment created by the single enantiomer covalently bonded to the dienophile has a remarkable effect only one enantiomer of the product is formed. 

In this chapter, we describe the isomerization, dimerization, and topochemical polymerization of benzyl muconates with various kinds of substituents on the benzyl ester group (Scheme 24.1), in order to reveal the solid-state reaction mechanism by the direct observation of crystal structures which change during the reactions. 

In more recent work involving a series of alkyl, aralkyl and arylamides of MTX and AMT [316], MeAPA was condensed with a-benzyl L-glutamic acid y-3,4-methylenedioxyanilide by the diethyl phosphorocyanidate coupling procedure to obtain the ester amide (VIII. 195). The benzyl ester group in (VIII.195) was then removed with NaOH to form (VIII.196) in 64% overall yield. Further reaction of (VIII.196) with boron tris(trifluoroacetate) in tri-fluoroacetic acid at 0 °C for 15 min afforded MTX y-(3,4-dihydroxyanilide) ((VIII.197) 79% yield). AMT y-amides (VIII.198)-(VIII.205) were prepared via the blocked intermediates (VIII.206)-(VIII.213), which were generated from FmAPA by the modified mixed anhydride route (four activation cycles ... 

The dibenzyl ester 27 can be obtained by slowly distilling a mixture of tartaric acid and benzyl alcohol, without adding an acidic catalyst34. It is a key intermediate in the synthesis of mono-O-acylated tartaric acids 28-31 33,35 the benzyl ester groups can be selectively cleaved to the free carboxylic acid groups by catalytic hydrogenation. Such derivatives form acyloxy-boranes with diborane which are used as chiral catalysts in enantioselective Diels-Alder reactions (Section D. 1.6.1.1.1.). 

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