1,2-Dimethoxyethane, purification

Lead dioxide as oxidizing agent for conversion of 2-hydroxy-3-methyl-benzoic add to 2-hydroxyiso-phthalic acid, 40, 48 Lithium aluminum hydride, in purification of 1,2-dimethoxyethane, 41, 97... 

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... 

Figure 1.6 ICH Class 2 solvents measured using GC. Purification of pravastatin sodium by preparative liquid chromatography. Reprinted from [15], copyright 2004, with permission from Elsevier. (Column 30 m X 0.53 mm i.d. 3 pm OVI-G43 (Supelco) carrier gas helium at 5 ml/min injection in split mode total flow 25 ml/min injector temperature 140 C flame ionization detector temperature 25C C and oven temperature 40°C for 20 min, to 240°C at 10°C/min, maintain at 240 C for 20 min. The components are 1 methanol, 3 acetonitrile, 4 dichloromethane, 5 hexane, 6 cw-l,2-dichloroeth-ylene, 7 nitromethane, 8 chloroform, 9 cyclohexane, 13 1,2-dimethoxyethane, 15 1,1,2-trichloroethyl-ene, 16 methylcyclohexane, 17 1,4-dioxane, 18 pyridine, 19 toluene, 20 2-hexanone, 21 chlorobenzene, 22 ethylbenzene, 23 m-xylene, 24p-xylene, 25 o-xylene, and 26 tetralin. The solvents are dissolved in DMF and heated at 80X for 60 min, and a sample of the headspace is injected.)...

Notes. (1) 1,2-Dimethoxyethane (Aldrich) is used without purification or drying. 

The 1,2-dimethoxyethane was obtained from Aldrich Chemical Company, Inc., and was allowed to stand over molecular sieves (type 4A in /i6-in. pellet form from Union Carbide Corporation) for several days. Final purification was accomplished by heating at reflux over potassium in a nitrogen atmosphere for at least 10 hr, followed by distillation from potassium. The solvent was used on the same day that it was distilled to minimize the formation of peroxides. 

A freshly opened bottle of reagent grade 1,2-dimethoxyethane (Aldrich Chemical Company, Inc.) was used without further purification. 

Dimethoxyethane, available from the Aldrich Chemical Company, Inc., was predried over calcium hydride and distilled from sodium/benzophenone prior to use. The solvent was used directly after purification or stored in an ampule bottle, available from the Aldrich Chemical Company, Inc., under a nitrogen atmosphere. 

Purification of commercial 9-BBN and other samples can be effected by recrystallization from 1,2-dimethoxyethane. Insoluble impurities can be removed from hot 1,2-dimethoxyethane solutions of 9-BBN by decantation of the solution to a second dry flask. To prevent clogging of the double-ended needle during the transfer process it is important to keep the ends of needle below the liquid surfaces. We have found that the receiver vessel should be charged with a small quantity of fresh, hot 1,2-dimethoxyethane prior to decantation and that a portion of this material should be transferred under a positive pressure of nitrogen to the 9-BBN solution to warm initially the transfer needle. Subsequently, the hot 9-BBN solution can be transferred without difficulty. 

The photoreactions are carried out in 50-100 mL of 1,2-dimethoxyethane or cyclohexane solutions, flushed with Ar (15 min) prior to irradiation, with 0.1 M enone and 0.5 M 2-trimethylsilyloxy-l.3-butadiene reaction temp 8-10°C (water-cooled reaction vessel) reaction time 40-48 h. The reactions are run in a Rayonet reactor equipped with RPR 3000- (quartz vessel used) or —3500 A lamps (Pyrex vessel used) and monitored by GC and TLC. Purification and separation of the product mixtures are performed by flash chromatography (silica gel, 50-fold). 

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