Hydroxy ethyl acetate

Hydroxy-l-naphthaldehyde [708-06-5] M 172.2, m 82 , b 192 /27mm, pKes, -7.8. Crystd from EtOH (1.5mL/g), ethyl acetate or water. 

Specialty waxes include polar waxes for more polar adhesive systems. Examples would be castor wax (triglyceride of 12-hydroxy stearic acid) or Paracin wax N- 2 hydroxy ethyl)-12-hydroxy stearamide) which are used in polyester, polyamide, or with high VA EVA copolymer-based systems. Other common polar waxes are maleated polyethylenes, which are used to improve the specific adhesion of polyethylene-based adhesives, and low molecular weight ethylene copolymers with vinyl acetate or acrylic acid, which are used to improve low temperature adhesion. High melting point isotactic polypropylene wax (7 155°C) and highly refined paraffin wax (7,n 83°C) are used where maximum heat resistance is critical. Needless to say, these specialty waxes also command a premium price, ranging from 2 to 5 times that of conventional paraffin wax. 

The combined aqueous washes are acidified with dilute hydrochloric acid and extracted with ethyl acetate. Evaporation of this extract yields 86 mg of 3a-hydroxy-ll-oxo-5j -etianic acid, mp 291-293° (dec.). 

Cyano-3 -hydroxy-5a-pregnan-20-one A suspension of 5a-pregnane-3, 20-dione (2 g) in ethanol (90 ml) is treated with acetone cyanohydrin (4 ml) and three drops of triethylamine and stirred at room temperature until complete dissolution. After 3 hr, the solution is diluted with 200 ml of water, acidified with acetic acid and the crystalline precipitate is thoroughly washed with water and dried under vacuum to give 2.1 g (97%) of product mp 172-178° (dec). A sample recrystallized from ethyl acetate melts at 176-179° (dec) [a]p 86° (ethyl acetate). 

Commercial Sodium Acetylide A suspension (30 ml) of sodium acete-lide (20% in exylene) is centrifuged and the solid brown sodium acetylide is taken up in 25 ml of dimethyl sulfoxide. To this is added a solution of 5 g of 5a-hydroxy-6j5-methylandrostane-3-17,dione 3-ethylene ketal in 85 ml of dimethyl sulfoxide. After stirring at room temperature overnight, ice is added and the solution diluted to about 250 ml. The tan precipitate is collected, washed with water and dried yield 4.8 g mp 202-204°. Crystallization from ethyl acetate gives a product of mp 204-206°. 

The mixture is distilled until most of the ether has been removed and then refluxed for 8 hr. Ethyl acetate is added to decompose the excess reagent and concentrated aqueous sodium sulfate is then added until the precipitate begins to adhere to the sides of the flask. Finally ca. 100 g of solid sodium sulfate is added, the salts are removed by filtration and washed well with dioxane. Evaporation of the solvent gives a solid residue which is dissolved in 60 ml of chloroform and shaken with 3.5 g of manganese dioxide for 16 hr. Subsequently another 3.5 g of manganese dioxide is added and shaking continued for a further 16 hr. The solid is removed by filtration and washed well with hot chloroform. Evaporation of solvent and crystallization of the residue from acetone-hexane affords 0.51 g (72%) of 17a-hydroxy-17jff-ethylandrost-4-en-3-one mp 145-148°. 

Preparation of 3a-Hydroxy-5) -pregn-17(20)-en-21-oic Acid . A solution of 15 g of 3a-acetoxy-5jS-pregnan-20-one in 290 ml of glacial acetic acid is treated with 13 g of bromine at room temperature. After complete addition of bromine the reaction mixture is heated at 40-50° for 30 min, and the product precipitated with water and filtered. The product is taken up in ethyl acetate (500-600 ml) and the resulting solution washed with dilute aqueous potassium bicarbonate. The solvent is concentrated in vacuo and the product crystallized from acetone to give 16g of dibromide mp, 173-175°. 

This nitrite (5 g) is dissolved in 200 ml of toluene and photolyzed For 2 hr at 20° as described above. Without further treatment the solution is chromatographed on 100 g of alumina and eluted with methylene dichloride containing increasing proportions of methanol. The first fraction gives 0.6g prednisolone BMD. The latter fractions afford 17,20 20,21-bismethylenedioxy-llj5-hydroxy-18-oximinopregna-l,4-dien-3-one (3 g) mp 270-274° [oc]d 0°, after crystallization from ethyl acetate-hexane. 

Irradiations of Testosterone Acetate (114), —In t-Butanol. 1.25 g of (114) in 250 ml t-butanol is irradiated for 32 hr at 30° under nitrogen with a Hanau Q81 high-pressure mercury lamp placed in a central water-cooled Pyrex immersion well with acetone filter. The solvent is evaporated in vacuo and the residue chromatographed on 125 g silica gel with benzene-ethyl acetate (4 1) to yield 0.29 g 17 -hydroxy-la,5 -cyclo-10a-androstan-2-one acetate [(118) 23%] mp 164-165°, after crystallization from acetone-hexane [a]i3 37 (CHCI3) 0.14 g cyclopentanone (120) (11%) mp 106-107° [aJo 38° (CHCI3) and 0.58 g starting material [(114) 46%]. Ratio (118) (120) - 2 1. 

Hydroxy-B-homo-5a-cholestan-7-one acetate (54b) A solution of 3/3-hydroxy-5a-cholestan-7-one acetate (51b 5 g mp 146-148°) in dioxane-ethanol (100 ml, 1 1) is placed in a 250 ml three-necked flask equipped with a mechanical stirrer and thermometer and is cooled to 0° (iee-salt bath). Powdered potassium cyanide (7.3 g) is added portionwise with stirring. Acetic acid (8 ml) is then added dropwise with constant stirring over 30 min. The resultant mixture is stirred for 1 hr at 0° C and for an additional 2 hr at room temperature. It is then poured into ice water (200 g ice, 100 ml water) and after standing for 1 hr the precipitate is collected by filtration. The product is dissolved in ether (100 ml), the ether solution is washed with 5% sodium bicarbonate, water and dried over anhydrous sodium sulfate. The filtrate is evaporated at reduced pressure and the solid residue (5.1 g) is crystallized from ethyl acetate (30 ml) to yield 2.8 g of cyanohydrin (52b) mp 160-164° repeated crystallization from the same solvent gives a product mp 164-167°. An alternative method of isolation of the cyanohydrin is used when 100 g or larger quantities are worked up. The reaction mixture is poured directly into a mixture of ice water and sodium bicarbonate, the precipitate (mp 155-156°) is washed well with water, dried and used directly for the next step. 

P-Hydroxy-A-norpregn-3(5)-en-2-one (7) A solution of the hydroxy-methylene steroid (5) (24.8 g) dissolved in 240 ml of acetic acid and 240 ml of ethyl acetate is ozonized at — 10° with one molar equivalent of ozone. The resulting solution is diluted with 240 ml. of water and 60 ml of 30 % hydrogen peroxide and allowed to stand overnight. The solution is diluted with 1.5 liters of water and extracted with 3 x 700 ml portions of ethyl acetate. The combined extracts are washed with water, saturated sodium chloride solution, dried over sodium sulfate and concentrated to dryness under vacuum, leaving 23.4 g of a colorless amorphous residue of crude diacid. This material shows a maximum in the ultraviolet spectrum at 224 mp (s 6,400) indicating a 53 % yield of unsaturated acid (6). It is used without further purification. 

It was reported that the Niemeiitowski synthesis of 4-hydroxy-3-iiitro-7-pheiiyl-l,8-iiaphthyridiii-2(lH)-oiie (25) from ethyl 2-amiiio-6-pheiiyhii-cotiiiate (23) and ethyl nitroacetate (24) in the presence of sodium was unsuccessful, producing only traces of (25), while condensation of ethyl 2-amino-6-phenylnicotinate (23) with the less reactive ethyl acetate resulted in the formation of 4-hydroxy-7-phenyl-l,8-naphthyridin-2(lH)-one in good yield [66JCS(C)315]. It seems that the more reactive nitroacetate tends to precipitate rapidly from the reaction mixture as its sodio derivative, which explains the low yield of (25). 

Cyclohexanone gives c-caprolactone, bp 102-10477 mm, which may polymerize on standing. The lactone may be converted easily to the corresponding e-hydroxy-hydrazide by heating on a steam bath with a slight excess of 100% hydrazine hydrate. The crude hydrazide may be recrystallized from ethyl acetate, mp 114-115°. 

Anschutz 1 treated aceto-salicylic chloride with sodium-malonic ester, with the formation of ethyl acetate and y3-hydroxy-coumarin-alpha-car-hoxylic ethyl ester—... 

The lactone is prepared as follows A solution of 5 parts of 17a-carboxyethyl-17/3-hydroxy-androst-4-en-3-one lactone and 5 parts of chloranil in 400 parts of xylene containing a trace of p-toluenesulfonic acid is heated at the boiling point of the solvent under reflux overnight. The solution is then cooled and filtered through approximately 200 parts of silica gel. The gel is successively washed with 5%, 10%, and 15% ethyl acetate-benzene... 

Benzhydryl 3Sodium hydride, 24 mg (4B mg of a 50% suspension of NaH in mineral oil, which has been washed with hexane to remove the oil), is added. When hydrogen evolution has ceased, 126 mg dimethyl sulfate is added. The solution is stirred for one hour at room temperature,diluted with 100 ml benzene and washed six times with water the last wash is made to pH B, if necessary, by adding sodium bicarbonate. The solution is dried over MgS04, filtered and evaporated, leaving benzhydryl 3eluting with 25 1 chloroform-ethyl acetate. 

The following technique is described in U.S. Patent 2,541,104. A solution of 2.0 g of 3(a )-hydroxy-21-acetoxy-11,20-diketo-pregnane, which can be prepared as described in Helv. Chim. Acta 27, 1287 (1944), is treated in a mixture of 25 cc of alcohol and 6.4 cc of acetic acid at 0°C with 6.0 g of potassium cyanide. The solution is allowed to warm to room temperature and after 3 hours is diluted with water. The addition of a large volume of water to the alcohol-hydrogen cyanide mixture precipitates a gum which is extracted with chloroform or ethyl acetate. The extract is washed with water, and evaporated to small volume under reduced pressure. The crystalline precipitate (1.3 g) consists of 3(a ),20-dihvdroxy-20-cvano-21-acetoxy-11-keto-pregnane dec. 175° to 185°C. 

The ether extract is evaporated to dryness to give about 500 mg of a crude product. From the ether solution there is obtained about 290 mg of yellow crystals, MP 220° to 236°C which is 17a,20,20,21-bis(methylenedioxy)-11 (3-formyloxy-2-hydroxy-methylene-6,16a-di-methyl-4,6-pregnadiene-3-one. The analytical sample is recrystallized from ethyl acetate and has a melting point of 249° to 255°C, [oIq -217°, I R 5.81 and 8.37 ji. From the mother liquor is obtained about 127 mg of 17a,20,20-21-bis(methylenedioxy)-11(3-hydroxy-2-hydroxymethylene-6,16a-dimethyl-4,6-pregnadiene-3-one. The analytical sample is recrystallized from ether and has a melting point of 200° to 204°C, [alo -197°, IR 6.05 to 6.2 and 6.4 jd. 

After evaporation of the solvent, a very thick, colorless oil is obtained. This base is dissolved by 200 ml of absolute ethanol and the quantity of HCI to obtain the dihydrochioride is added. It is left for a few hours over ice, dried, washed with approximately 100 ml of anhydrous ether in order to obtain 190 to 195 grams of 1-[2-phenyl-2-methoxy]-ethyl-4-[3-phenyl-3-hydroxy] -propyl-piperazine dihydrochioride after drying at 60°C in vacuo. The yield is 80%. It is recrystallized from absolute ethanol. The product is in the form of white crystalline powder, soluble in water, slightly soluble in alcohol, insoluble in ethyl acetate. 

To 6a-fluoro-16a-hydroxy-hydrocortisone 21-acetate, described by Mills et al, J. Am. Chem. Soc., volume 81, pages 1264 to 1265, March 5, 1959, there was added acetic anhydride in dry pyridine. The reaction mixture was left at room temperature overnight and was then poured with stirring into ice water. The resulting precipitate was filtered, washed with water and crystallized from acetone-hexane to give 6a-fluoro-16a-hydroxy-hydrocortisone-16a,21-diacetate. This was reacted with methane-sulfonyl chloride in dimethyl formamide in the presence of pyridine at 80°C for 1 hour. The mixture was cooled, diluted with water and extracted with ethyl acetate. The extract was washed with water, dried over anhydrous sodium sulfate and the ethyl acetate was evaporated. By recrystallization of the residue from acetone-hexane there was obtained 6a-fluoro-A <" -pregnadiene-16o ,17a,21-triol-3,20-dione 16a,21 diacetate. 

A mixture of 290 mg of the 16,21-diacetate of 6a,9a-difluoro-16o --hYdroxY-hYdrocortisone, 30 cc of t-butanol, 0.5 cc of pyridine and 150 mg of selenium dioxide was refluxed for 53 hours under an atmosphere of nitrogen and cooled ethyl acetate was added and filtered through celite the solvent was evaporated to dryness under reduced pressure, the residue... 

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