Hydrolysis ethers

It is obvious that the primary amines formed in this reaction will be uncontaminated by secondary or tertiary amines (unlike 10-44). The reaction is usually rather slow but can be conveniently speeded by the use of a dipolar aprotic solvent such as DMF or with a crown ether. Hydrolysis of the phthalimide, whether acid or base catalyzed (acid catalysis is used far more frequently), is also usually very slow, and better procedures are generally used. A common one is the Ing-Manske procedure,in which the phthalimide is heated with hydrazine in an exchange... 

The mechanism of enamine hydrolysis is thus similar to that of vinyl ether hydrolysis (10-6). 

An interesting synthesis of enantiopure cu-decahydroquinolines, which involves enol ether hydrolysis, double bond isomerization, and intramolecular 1,4-addition of an amino group across a cyclohexenone has been reported <06T9166>. The process is stereoselective, with the exclusive formation of both cu-isomers 176 (43% over 3 steps) and 177 (17% over 3 steps) of the decahydroquinoline ring. 

While aromatic nitro and azoxy compounds have been reduced to azo compounds with lithium aluminum hydride, aliphatic nitro compounds produced only the corresponding aliphatic amines [65]. The usual technique involves dropwise addition of 1 mole of nitro compound in ether to 1.05-1.15 moles of lithium aluminum hydride in ether solution at Dry Ice temperatures followed by warming to room temperature. If the resulting product is only slightly soluble in ether, hydrolysis should be carried out with dilute sulfuric acid. Then the azo compound simply needs to be filtered off, washed with water, and dried. If the product is ether-soluble, the ether layer is separated, evaporated, and the residue is recrystallized [65, 66]. 

Desilylation of silyl eno ethers. Hydrolysis of silyl enol ethers of aldehydes with oxalic acid in aqueous fill can result in partial degradation to a ketone (equation... 

Ethyl enol ethers of acyl silanes have been prepared by the palladium-mediated addition of silyl stannanes to alkynyl ethers. Hydrolysis using trifluoroacetic acid gave very high yields of acyl silanes (vide supra, Section m.A.4)82. 

Studies of vinyl ether hydrolysis have demonstrated a strong retardation effect of jS-carboxy and /J-carbomethoxy groups (2000- to 25,000-fold). The rate profile for (Z)-/5-met boxy methacry lie acid indicates that ionization of the carboxylate raises the rate of hydrolysis by a factor of 240. It has been proposed that this difference in reactivity of ionized and non-ionized forms of the substrate is due to the conjugative and inductive effect of the substituents, rather than /5-lactone formation65,66. 

Figure 8-8. The copper-mediated conversion of an anisole derivative to a co-ordinated phenoxide. This provides a useful alternative to conventional methods of ether hydrolysis, which involve treatment with Lewis acids such as boron tribromide, hydriodic acid or pyridinium chloride.

Ether hydrolysis is observed for the API timolol maleate. Under pH 5 aqueous autoclave conditions (120°C), three degradants were isolated. 

Step 2 Mild acid catalyzes the enol ether hydrolysis without subsequent 3, y to a, (3 alkene isomerization. 

Step 2b Silyl ether hydrolysis followed by hemiacetal equilibration leads to the keto-alcohol. Step 2 is a modified Rubottom reaction Org. Synth. 1985, 64, 118). 

Insoluble in water, but readily soluble in acid or alkali soluble in benzene and ether. Hydrolysis in aqueous and alkaline solutions leads to replacement of Cl atoms by OH forming the hydroxy form.2... 

Ethyl vinyl ether hydrolysis 0-66 Kreevoy and Eliason, unpublished... 

Another approach to the problem of the value of n is to determine the degree of hydration of the transition state in an aprotic, nearly anhydrous, solvent. This has been done (Williams and Kreevoy, unpublished data) for ethyl vinyl ether hydrolysis in dimethylsulfoxide (DMSO). In nearly anhydrous DMSO containing very low concentrations of hydro-... 

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