Methyl ethers purification

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

The synthesis and purification of cumyl alcohol (CumOH), p-dicumyl methyl ether (DCE)) and 2-chloro-2,4,4-trimethylpentane (TMPC1), and the sources and purification of methyl chloride (MeCl), methylcyclohexane (MCHx), isobutylene have been described [9, 10]. P-Pinene (P-PIN), (Aldrich), was chromatographed over alumina (activity I, Fisher), and freshly distilled over CaH2 under nitrogen according to 1H-NMR spectroscopy and GC analysis the purity was >99%. 2,6-Di-/er/-butylpyridine (DtBP), (Aldrich), anhydrous A,A-dimethylacetamid (DMA), (Aldrich), ethylaluminum dichloride (EtAlCl2), 1.0 M solution in hexanes (Aldrich), and methanol (Fisher) were used as received. 

All solvents used for general applications were of reagent grade. For special purposes, purification of solvents was effected using standard procedures. All other reagents were used as supplied commercially except as noted. A solution of chloromethyl methyl ether (6 mmole/mL) in methyl acetate was prepared by adding acetyl chloride (141.2 g, 1.96 mol) to a mixture of dimethoxy methane (180 mL, 2.02 mol) and anhydrous methanol (5.0 mL, 0.12 mol).20 The solution was diluted with 300 mL of 1,1,2,2-tetrachloroethane and used as a stock solution for the chloromethylation experiments. 

The action of diazomethane in aqueous 1,2-dimethoxyethane on 4-methoxy-l-/3-D-ribofuranosyl-2(lf/)-pyrimidinone gave, after purification, the corresponding 2 -methyl ether in 37% yield.333 N.m.r. spectroscopy showed that the crude mono-O-methyl fraction contained the 2 - and 3 - isomers in the ratio of 7 2. The 2 -methyl ether proved to be a versatile intermediate, as acid hydrolysis yielded 2 -0-methyluridine, whereas reaction with ammonia or methylamine... 

The beneficial effect of the change of the flow rate of the mobile phase has also been exploited for the improvement of CCC purification of the components of the dye Quinoline yellow (Colour Index No. 47005). The chemical structures of the components of Quinoline yellow are shown in Fig. 3.121. The two-phase system used for the purification consisted of tm-butyl methyl ether-l-butanol-ACN-0.1 M TFA (1 3 1 5 v/v). The column... 

Alternatively, solvent partition or countercurrent techniques may be applied. In order to obtain an isoflavonoid-rich fraction from Erythrina species (Leguminosae) for further purification work, an organic solvent extract was dissolved in 90% methanol and first partitioned with hexane. The residual methanol part was adjusted with water to 30% and partitioned with t-butyl methyl ether-hexane (9 1). This latter mixture was then chromatographed to obtain pure compounds. ... 

Clinical trials of these orally active progestins showed that they were effective as contraceptives with a success rate that exceeded 99%. These compounds were then marketed as obtained from the reaction sequence after appropriate purification. As the analytical methodology improved it became apparent that a small amount of an impurity was present in all active samples. An examination of the reaction scheme allowed ready identification of that by-product. Any unreduced estradiol methyl ether (13-1) will go to estrone methyl ether on oxidation this will then afford the potent orally active estrogen mestranol (9-1) on ethynylation. Subsequent... 

Dichloromethyl methyl ether (98%) was purchased from Aldrich Chemical Company, Inc. (listed as a, a-dichloromethyl methyl ether), and used without purification. Better results can be obtained if the material is distilled under nitrogen prior to use. Unlike chloromethyl methyl ether and bis(chloromethyl) ether, dichloromethyl methyl ether is reported to have no significant carcinogenic activity.6 However, as a precaution it should be handled carefully in a well-ventilated hood. 

An alternative cleanup procedure is the partition of the raw extract, which often contains considerable amounts of lipid material, between an organic and an aqueous sodium hydroxide phase. With this partitioning scheme, the analytes are further fractionated into estrogens and nonestrogens. The presence of phenolic groups in the molecules of estrogens such as diethylstilbestrol and zeranol ensures their complete extraction from organic phases such as chloroform or tert.-butyl methyl ether into the aqueous sodium hydroxide phase (435, 438, 447). Further purification could be accomplished by neutralization of the sodium hydroxide solution and back-extraction of the contained diethylstilbestrol into diethyl ether (435), or adjustment of the pH of the sodium hydroxide solution to 10.6-10.8 and back-extraction of the contained zeranol into a chloroform phase (447). 

The methyl ether of cellulose has a methoxyl content which varies between 6 and 33 %. Methylcellulose can be prepared by the action of methyl chloride or methyl sulfate on cellulose that has been previously treated with alkali. Purification is accomplished by washing the reaction product with hot water. The degree of methylation can be controlled to yield products with varying viscosities. Seven viscosity types of methylcellulose are currently produced with centipoise values ranging from 10 to 4000. Methylated cellulose of low methoxy content is soluble... 

A] Typical Procedure for the Hydrolysis of Methyl Ethers and Ion-Exchange Purification of the Final Amino Acids (Scheme 12)f21... 

Recently, it has been reported101 that mt/o-inositol reacts rapidly and stoichiometrically with periodate at 50-65°. If the excess periodate is determined spectrophotometrically,102 a sensitive and convenient micromethod results (range 2-70 jug.). That this method will become the one of choice for m/o-inositol seems probable. It should be applicable to the other inositols, and, perhaps, with some modifications, to inositol methyl ethers, quercitols, etc. Most interfering substances are effectively removed by vigorous treatment with hot, concentrated hydrochloric acid,101(a) sulfuric acid,103 or barium hydroxide,101[Pg.158]

The carbonium ion salt obtained in this manner reacted with methanol to give the methyl ether, (OC) 9( )o3CC (C H3) 2OCH , in 86% yield and with aniline to produce (OC)9Co3CC(CH3)2NHC6H5 in 49% yield. Attempted purification of the methyl ether by chromatography on pH4 silicic acid re-... 

Methylated derivatives are also highly soluble in water. The major methylated derivatives are the 2,6-dimethyl, 2,3,6-trimethyl and randomly methylated derivatives. The dimethyl and trimethyl derivatives are the derivatives most frequently described in the literature. The main advantage of the randomly methylated derivatives is lower cost. Production of the dimethyl and trimethyl derivatives involves several purification steps. Due to the random substitution and mixture of constituents, the randomly substituted derivatives are more soluble than the dimethyl and trimethyl derivatives. All methyl ethers have a decreased solubility at higher temperatures, similar to the behavior of other methylated carbohydrates. 

Although the GC separation of methyl ethers [16] of phenols has been described, these derivatives are nowadays mainly employed only in special instances, e.g., for increasing the sensitivity of the analysis. The determination of chlorinated phenols in spent bleach liquors from paper mills was reported by Lindstrom and Nordin [17]. A water sample was extracted stepwise with diethyl ether at various pH values, after preliminary purification by means of HPLC, phenols were converted into ethyl ethers by reaction with diazoethane in isooctane—ethanol (9 1) and good reproducibility was achieved. 

THF was freshly distilled from sodium/benzophenone. tert-Butyl alcohol was purchased from Aldrich Chemical Company. Inc., and was used without further purification. Solvents for extraction and chromatography were technical grade and distilled from the indicated drying agents hexane (CaC ) dichloromethane (CaC ) tert-butyl methyl ether (MTBE) (CaSOyFeSCXt) ethyl acetate (K2CO3). 

Preussomerin I 697 and ( )-preussomerin G 698 were obtained from 620 with a five- and six-steps sequence in 15% and 12% overall yield, respectively, through modifications of substituents of the dioxocin ring. Thus, attack of lithium methoxide from the less hindered face of the enone 620, followed by protection of the phenolic oxygen as its methyl ether provided the methoxy adduct 692. The ketone 693 was obtained through a benzylic bromination-solvolysis-oxidation protocol, which required only a single purification. The C(2)-C(3) olefin was introduced by selective silylation of the C-l carbonyl of diketone 693 and oxidation of the silyl enol ether with Pd(OAc)2. Enone... 

Aryl-2-methoxy-l,3-dithioles regenerate the starting salts in quantitative yield by addition of acids. Therefore purification of the salts through their 2-methyl ethers is very effective and 2-methyl ethers can be used instead of salts in acidic medium. ... 

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