Ethers methoxymethyl, alcohol

Protection of tertiary alcohols. Methylthidiiiethyl (MTM) ethers have the advantage that they can be prepared from tertiary alcolols (7,135), but the disadvantage that they are prone to oxidation. They can be convcrtcil into 2-mcthoxycthoxymethyl (MEM) ethers, methoxymethyl (MOM) ethers, or ethoxy methyl (EOM) ethers by reaction with... 

Methoxymethyl ethers. Methoxymethylation of alcohols can be carried out in high yield by reaction with methylal at 25° in chloroform catalyzed by phosphorus pentoxide. These ethers are preferable to tetrahydropyranyl ethers... 

Silyl ether protected alcohols (eq 5) have been converted directly into the corresponding bromides with PhaP and CBr4. The reaction works best if 1.5 equiv of acetone are added. Tetrahy-dropyranyl ether protected alcohols have also been directly transformed into the bromides using this reagent combination. The reaction has been reported to proceed with inversion of configuration (eq 6). If unsaturation is appropriately placed within a tetrahydropyranyl (eq 7) or a methoxymethyl (eq 8) protected alcohol, cyclization occurs to afford tetrahydropyrans. The conversion of an alcohol to the bromide without complications with a methoxymethyl protected alcohol in the molecule is possible (eq 9).i ... 

Methoxymethylation of alcohols is generally achieved through alkylation with chloromethyl methyl ether. The procedure described here for the preparation of Bu3SnCH20CH20CH3 avoids the use of the highly toxic chloromethyl ether by employing an acid-catalyzed acetal exchange reaction with dimethoxymethane for the... 

Methoxyethanol, see Methyl cellosolve 2-Methoxyethanol acetate, see Methyl cellosolve acetate 2-Methoxyethyl acetate, see Methyl cellosolve acetate 2-Methoxyethyl alcohol, see Methyl cellosolve 2-Methoxyethyl ethanoate, see Methyl cellosolve acetate Methoxyhydroxyethane, see Methyl cellosolve Methoxymethyl methyl ether, see Methylal 4-Methoxyphenylamine, see p-Anisidine... 

The benzyl ether is prepared in a similar manner to the methoxymethyl ether, that is, by reaction of the conjugate base of the alcohol with benzyl bromide in an SN2 reaction. An example of a sequence that employs a benzyl ether protecting group is illustrated in the following sequence ... 

One of the mildest methods for preparing methylene acetals involves reaction of a diol with dimethoxymethane in the presence of a suitable activating agent such as phosphorus pentoxide,176 trimethylsilyl Inflate.177 or lithium bromide and p-toluenesulfonic acid.178 The reaction is also used to make methoxymethyl ethers (see section 4.4,1) from alcohols. Scheme 3,95 illustrates the simultaneous formation of a methoxymethyl ether and a methylene acetal from Shikimic Acid.169 The reaction was adapted to the synthesis of the methylene acetal moiety of the marine antitumour agent Mycalamide B [Scheme 3.96],179... 

A mild procedure for the appendage of MOM groups to acid-sensitive substrates is illustrated by the protection of the allylic alcohol in Avermectin derivative 259.1 using [(methoxymethyl)thio]-2-pyridine (259 2) sitver(I) Inflate and sodium acetate in THF at room temperature [Scheme 4.259],479 Primary secondary and tertiary alcohols and phenols are methoxymethylated in good yield though phenols are slower to react. Reagent 259.2 (bp 66 °C/0.088 kPa) is easily prepared in 75% yield by the reaction of pyridine-2-thiol with dimethoxy-methane activated by trifluoroborane etherate. 

This procedure consists of the synthesis of a precursor, methoxymethyl vinyl ether, an a-hydroxy enol ether, and the intramolecular hydrosilylatlon of the latter followed by oxidative cleavage of the silicon-carbon bonds. The first step, methoxymethylation of 2-bromoethanol, is based on Fujita s method.7 The second and third steps are modifications of results reported by McDougal and his co-workers. Dehydrobromination of 2-bromoethyl methoxymethyl ether to methoxymethyl vinyl ether was achieved most efficiently with potassium hydroxide pellets -9 rather than with potassium tert-butoxide as originally reported for dehydrobromination of the tetrahydropyranyl analog.10 Potassium tert-butoxide was effective for the dehydrobromination, but formed an adduct of tert-butyl alcohol with the vinyl ether as a by-product in substantial amounts. Methoxymethyl vinyl ether is lithiated efficiently with sec-butyllithium in THF and, somewhat less efficiently, with n-butyllithium in tetrahydrofuran. Since lithiation of simple vinyl ethers such as ethyl vinyl ether requires tert-butyllithium,11 metalation may be assisted by the methoxymethoxy group in the present case. 

After deprotection of the methoxymethyl (MOM) ether under acidic conditions, alcohol 319 was deoxygenated through the Barton procedure to obtain the natural alkaloid (—)-pyrinodemin A (Scheme 72) <20030L2611>. 

Cs-X has also been used to promote the selective O-methylation of phenol with dimethyl carbonate. 2 N-Monomethylaniline was obtained in 93% yield by reacting aniline with dimethyl carbonate over a K-Y catalyst at 180°C (Eqn. 22.46). 3 The reaction of alcohols with chloromethyl ether over Na-Y gave the resulting methoxymethyl ethers in 70%-90% yields (Eqn. 22.47). 4... 

Methoxymethyl ethers. Etherification of alcohols is readily achieved by refluxing them with graphite in methylal. 

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