Acetic acid, ethyl ester, purification

As a chemical raw material, ethanol is used for the production of a range of monomers and solvents, and is essential in pharmaceutical purification. In the presence of an acid catalyst ethanol reacts with carboxylic acids to produce ethyl esters. The two largest-volume ethyl esters are ethyl acrylate (from ethanol and acrylic acid) and ethyl acetate (from ethanol and acetic acid). Ethyl acrylate is a... 

Triphenylphosphine (342 mg, 1.30 mmol) was added in one portion to a solution of 4-acethylamino-5-azido-3-(l-ethyl-propoxy)-cyclohex-l-ene-l-carboxyllic acid ethyl ester (272 g, 0.80 mmol) in THF (17 ml) and water (1.6 ml). The reaction was then heated at 50°C for 10 h, cooled and concentrated in vacuo to give a pale white solid. Purification of the crude solid by flash chromatography on silica gel (50% methanol in ethyl acetate) gave 242 mg (96%) of the 4-acethylamino-5-amino -3-(l-ethyl-propoxy)-cyclohex-l-ene-l-carboxyllic acid ethyl ester as a pale solid. 

It is suitable, not only for rose odours, but also for blending with almost any flower oil. Phenyl-ethyl alcohol forms a solid compound with chloride of calcium, which is very useful for its purification. On oxidation it is converted into a mixture of phenyl-acetaldehyde and phenyl-acetic acid. The last-named body forms an ethyl ester melting at 28°, which serves for its identification. 

To a stirred solution of dry N,N-diisopropylamine (1.1 ml, 7.85 mmol) in THF (10 ml) cooled to 0°C was added nBuLi (2.5 M in hexanes, 3.14 ml, 7.85 mmol) over several min. After the solution was stirred for 10 min following the addition, the reaction mixture was cooled to -78°C, and an additional 1 ml of THF was added. The acetic acid (+)-6-ethyl-5-methyl-2-(l-methyl-l-hydroxy-2-buten)-yl-3,6-dihydro-2H-pyran ester (1.65 g, 6.54 mmol) in THF (7 ml) was slowly added over a 40 min-period at -78°- (-70)°C. After the reaction was stirred for 5 min, TBSCI (1.18 g) in THF-HMPA (1 1,6 ml) was added in one portion. The cooling bath was then removed, and the reaction mixture was allowed to warm to 0°C and stirred for 1 h, then at room temperature for an additional 1 h, and finally 1.5 h at 65°C. The yellow solution was cooled to room temperature and diluted with THF (60 ml), then treated with a 10% HCI aqueous solution (16 ml). The reaction mixture was stirred at room temperature for 3 h The solvent was evaporated and the residue diluted with Et20 and treated with a 1.0 N KOH aqueous solution the organic phase was discarded, and the aqueous solution was washed with Et20. The basic solution was acidified with 10% HCI and the product isolated by ether extraction. This afforded 1.0 g (61%) of a 12 1 mixture of (+)-6-ethyl-5-methyl-2-(3-methyl-hex-4-enoic acid)-3,6-dihydro-2H-pyran as a colorless oil. This mixture was carried through the next reaction without further purification. 

To a solution of 5-methoxymethoxy-7-oxa-bicyclo[4.1.0]hept-3-ene-3-carboxylic acid methyl ester (4.9 g, 22.9 mmol) in 8/l-Me0H/H20 (175 ml, v/v) was added sodium azide (7.44 g, 114.5 mmol) and ammonium chloride (2.69 g, 50.4 mmol) and the mixture was refluxed for 15 h. The reaction was diluted with water (75 ml) to dissolve precipitated salts and the solution was concentrated to remove methanol. The resulting aqueous phase containing a precipitated oily residue was diluted to a volume of 200 ml with water and was extracted with ethyl acetate (3 times 100 ml). The combined organic extracts were washed with saturated NaCI (100 ml), dried (MgS04), filtered and evaporated. The crude was purified on silica gel (1/1-hexane/ethyl acetate) to afford 5-azido-4-hydroxy-3-methoxymethoxy-cyclohex-l-ene-l-carboxylic acid methyl ester (5.09 g, 86%) as a pale yellow oil. Subsequent preparations of 5-azido-4-hydroxy-3-methoxymethoxy-cyclohex-l-ene-l-carboxylic acid methyl ester provided material which was of sufficient purity to use in the next step without further purification. 

A mixture of calendic acid methyl ester 1 (3 mmol, 1.50 g) and maleic anhydride (5 mmol, 0.49 g) was heated for 2h at 150 °C under nitrogen. The reaction was followed by thin-layer chromatography [petroleum ether-diethyl ether (7 3), Rf 1=0.60, Rf 3=0.23], Purification of product 3 was achieved by column chromatography [silica gel using petroleum ether/diethyl ether (7 3) and petroleum ether/ethyl acetate (1 1) as eluent]. Fractions containing product 3 were collected and the solvent was removed in vacuo. Compound 3 was recrystallized from petroleum ether/diethyl ether (4 1). 

Alkylation of diisopropyl (7 )-malate with benzyl bromide produces a 10 1 mixture of benzylated product 945 in 80—85% yield. Use of the isopropyl ester results in higher yields than in the case of the corresponding methyl or ethyl esters, presumably due to reduced ester— enolate condensation. Purification of the diastereomeric mixture is accomplished by hydrolysis to diacid 946 and recrystallization from either chloroform or ethyl acetate/hexane [52% overall yield from diisopropyl (i )-malate]. Treatment of 946 with acetyl chloride and subsequent reaction with isopropyl alcohol gives monoester 948 in 95% overall yield. Amidation of the free acid followed by Hofmann degradation affords 950 in 90% overall yield. Removal of the Boc group and hydrogenation of the benzene ring provides 952. 

To a solution of 10.7 g L-methionine ethyl ester hydrochloride (0.05 mol) in 200 mL THF was added 7.0 mL triethylamine (0.05 mol). The resulting salt was filtered. To the solution, 17.0 g (0.055 mol) Nps-leucine NCA was added and stirred at room temperature for 2 h. Then the solvent was evaporated under reduced pressure at 35°C, the residual oil was dissolved in 200 mL ethyl acetate, and the solution was washed with 5% of citric acid, 5% of sodium bicarbonate, and water and dried over Na2S04. The solution was concentrated in vacuum at 40°C to give an oil, which was crystallized by adding n-hexane. Further purification can be done from recrystallization in ethyl acetate. 

This procedure for the synthesis of ethyl 3-nitroacrylate is essentially that of Stevens and Emmons.2 Four major changes have been introduced by the submitters rapid introduction of dinitrogen tetroxide no purification of the intermediate nitro iodo ester use of dry, finely powdered sodium acetate for elimination of hydroiodic acid and percolation of the final product through a mat of alumina. With these modifications, the preparation is reproducible and highly efficient (80-90% overall). 

Cuscutic resinoside A (1 tetradecanoic acid, (115)-[[6-deoxy-3-(9-(6-deoxy-a-L-mannopyranosyl)-4-0-[(2/ ,3R)-3-hydroxy-2-niethyl-l-oxobutyl]-a-L-nianno-pyranosyl]oxy]-intramol. l,2 -ester) was obtained from the ethyl acetate-soluble fraction of a methanol extract prepared from the seeds of Cuscuta chinensis Lam. The purification of this compound employed a combination of column and preparative-scale HPLC. The structure was deduced from spectroscopic evidence and acid hydrolysis 14). The degradative process gave convolvuUnolic acid, nilic acid, and L-rhamnose. The sugar components were identified by GC analysis after being converted to their thiazolidine derivatives. This disaccharide has a unique macrocyclic lactone, which is placed between C-1 and C-2 of the first rhamnose moiety. 

If hydrolysis of the methyl ester of the Laas is required, this can be achieved by dissolving the compound in DME and water and adding LiOH (-5 equivalents) and allowing the reaction to stir at room temperature overnight. The reaction mixture is then acidified to pH 4.0 with 5% citric acid solution and extracted into ethyl acetate (3 x 20 mL). The organic extracts are washed with saturated NaCl, dried with MgS04, filtered, and solvent removed. The purification of the resulting free acid depends on the compound to which the Laa has been coupled. 

When treated with concentrated alkali, acetoacetic ester is converted into two moles of sodium acetate, (a) Outline all steps in a likely mechanism for this reaction. (Hint See Sec. 21.11 and Problem 5.8, p. 170.) (b) Substituted acetoacetic esters also undergo this reaction. Outline the steps in a general synthetic route from acetoacetic ester to carboxylic acids, (c) Outline the steps in the synthesis of 2-hexanone via acetoacetic ester. What acids will be formed as by-products Outline a procedure for purification of the desired ketone. (Remember that the alkylation is carried out in alcohol that NaBr is formed that aqueous base is used for hydrolysis and that ethyl alcohol is a product of the hydrolysis.)... 

Concerning the purification of the add-esters, it may be mentioned, that the crude reaction-product is shaken with a sodium carbonate solution until the ester no longer shows an acid reaction. The alcohol may be removed from esters difficultly soluble in water by repeatedly washing with water in case an ester is moderately soluble In water, as ethyl acetate, it is better to use a solution of caldum chloride... 

A solution of this ester (8.35 g, 21.6 mmol, 1.0 equivalents) in tetrahydrofuran (THF 100 mL) was cooled to 0 °C, and pyridinium p-toluenesulfonate (PPTS, 500 mg, 2.00 mmol, 0.1 equivalents) and then 2,2-dimethoxypropane (20.0 mL, 163 mmol, 5.9 equivalents) were added. The cold bath was removed and the mixture was stirred at room temperature for 48 h, quenched with saturated aqueous NaHCOs solution, and extracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated. Purification by chromatography on SiO2 (3% ethyl acetate and 1% triethylamine in hexanes, and then 100% EtOAc) afforded the acetonide and a small amount of starting diol which was re-subjected and purified as above. The two batches were combined to afford naphthalene-2-carboxylic acid 2-[(4S)-2,2- dimethyl-[l,3]dioxan-4-yl]-2-methylpropyl ester (9.140 g, 97%) as a clear colorless syrup. Reference Wipf, P Graham, T. H.,/. Am. Chem. Soc. 2004,126, 15346-15347. 

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