Organic solutions, anhydrous

Preparation of l9-Norandrost-A-ene-3, l-dionef A solution of 1.1 g of 10y5-cyano-19-norandrost-5-ene-3,17-dione bis-ethylene ketal in a mixture of 15 ml of ethanol and 15 ml of toluene is carefully added to a vigorously stirred suspension of 10 g of sodium in 150 ml of boiling toluene. The addition is regulated to maintain the reaction mixture at the boiling point of the solvent. Another 40 ml of anhydrous ethanol is then added at the same rate. The solution is cooled and the excess of sodium is decomposed by addition of 95% ethanol. The reaction mixture is then diluted with water, the toluene layer separated and the aqueous phase extracted twice with ether. The organic solution is washed with water, dried and evaporated to yield 1 g of an amorphous mixture of the bis-ethylene ketals of 19- norahd-rost-5- and -5(10)-ene-3,17-dione (Note 1). 

The trialkylborane is oxidized by the addition to the stirred reaction mixture of 32 ml of a 3 solution of sodium hydroxide, followed by the dropwise addition of 32 ml of 30 % hydrogen peroxide at a temperature of 30-32° (water bath). The reaction mixture is saturated with sodium chloride and the tetrahydrofuran layer formed is separated and washed with saturated sodium chloride solution. The organic solution is dried over anhydrous magnesium sulfate and the THF is removed. Distillation affords 24.5 g (80%) of 4-methyl-1-pentanol, bp I51-153°/735 mm. 

A solution of 88.5 parts of L-phenylalanine methyl ester hydrochloride in 100 parts of water is neutralized by the addition of dilute aqueous potassium bicarbonate, then is extracted with approximately 900 parts of ethyl acetate. The resulting organic solution is washed with water and dried over anhydrous magnesium sulfate. To that solution is then added 200 parts of N-benzyloxycarbonyl-L-aspartic acid-a-p-nitrophenyl, -benzyl diester, and that reaction mixture is kept at room temperature for about 24 hours, then at approximately 65°C for about 24 hours. The reaction mixture is cooled to room temperature, diluted with approximately 390 parts of cyclohexane, then cooled to approximately -18°C in order to complete crystallization. The resulting crystalline product is isolated by filtration and dried to afford -benzyl N-benzyloxycarbonvI-L-aspartyl-L-phenylalanine methyl ester, melting at about 118.5°-119.5°C. 

Methyl ethyl (7-methoxy-10-methyl-3-phenthiazinyl)malonate (62.2 grams) followed by methyl iodide (45.7 grams) is added to a solution of sodium (4.45 grams) in anhydrous ethanol (500 cc). The reaction mixture is heated under reflux for 1 hour at 45°C, then for 6 hours at 55°C, and finally concentrated to dryness under reduced pressure (20 mm Hg). The residue is taken up in methylene chloride (300 cc) and water (250 cc), filtered in the presence of a filtration adjuvant, washed with methylene chloride (150 cc) and water (150 cc), and decanted. The aqueous solution is extracted once again with methylene chloride (100 cc), and the combined organic solutions washed with water (100 cc), aqueous 0.1 N sodium hyposulfite solution (200 cc) and finally with water (200 cc). After drying over anhydrous sodium sulfate and evaporation to dryness under reduced pressure (20 mm Hg), there is obtained an oil (64.8 grams) which is dissolved in methylene chloride (100 cc) and... 

The decanted aqueous phase was extracted three times with a total of 150 ml of ethyl acetate. The combined organic solutions were filtered over Clarcel and extracted three times with a total of 150 ml of an Iced normal aqueous methane-sulfonic acid solution. The combined acid extracts were rendered alkaline on an ice bath with 30 ml of ION caustic soda solution. The separated oil was extracted four times with a total of 200 ml of ether. The combined ethereal extracts were washed twelve times with a totai of 360 ml of distilled water, dried over anhydrous magnesium sulfate in the presence of 0.3 g of animal charcoal and evaporated under reduced pressure on a water bath at 40°C. The oily residue obtained (3.8 g) was dissolved in 30 ml of boiling acetonitrile. After cooling for 2 hours at 3°C, the crystals formed were separated, washed with 5 ml of acetonitrile and dried at ambient temperature at low pressure. 

The reaction mixture is poured into a separatory funnel containing about 0 S kg. of crushed ice and is shaken thoroughly. The organic layer is separated, and the aqueous solution is extracted with two SO-ml. portions of methylene chloride. The combined organic solution is washed three times with 75-ml. portions of water A crystal of hydroquinone is added to the methylene chloride solution (Note 1) which is then dried over anhydrous sodium sulfate. After evaporation of the solvent, the residue is distilled to give the crude product, b p. 68-74° (0.9 mm.). After redistillation there is obtained 60-66 g. (81-89%) of mesitaldehyde b.p. 113-115° (11 mm.), 20d 1.5538. 

Electropolishing region does not occur in anhydrous organic solutions due to the lack of water which is required for the formation of oxide film. Figure 5, as an example, shows that in anhydrous HF-MeCN solution the current can increase with potential to a value of about 0.5 A/cm2 without showing a peak current. The relationship between current and potential is linear due to the rate limiting effect of resistance in solution and silicon substrate. 

The phenol (21.3 mmol), epichlorohydrin (0.17 mol), anhydrous K2CO, (5.9 g, 42.6 mmol) and TBA-MeCHOHCH2OSO, (0.2 g, 0.5 mmol) are stirred for 90 min at 75-80°C until the reaction is complete, as shown by TLC analysis. The mixture is cooled to room temperature and the mixture is filtered. The residue is washed with epichlorohydrin and the combined organic solution is fractionally distilled to yield the aryloxymethyloxirane (85-93%). 

Method B with tertian alcohols Anhydrous Na2CO, (30 g) is added to the alcohol (0.1 mol) and TEBA-CI (2.3 g, 10 mmol) in CH,C12 (50 ml), followed by the acid chloride (0.1 mol). The stirred mixture is refluxed for ca. 3 h and then filtered. The residue is extracted with CH2C12 (10 ml) and the combined organic solution is washed well with H,0 until neutral, dried (CaS04), and fractionally distilled. 

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