Ethyl acetate hexane

Chloroform with acetic acid, acetone, benzene, ethanol, ethyl acetate, hexane, methanol or pyridine. Cyclohexane with acetone, benzene, carbon tetrachloride, ethanol or diethyl ether. 

Recrystd three times from a mixture of ethyl acetate/hexane (5 1) or MeOH/pet ether, then stored at 95° for 48h... 

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. 

POCI3 was added to a solution of amide 62 (0.075g, 0.02 mmol) in toluene (5 mL). The reaction mixture was heated to 110 °C with stirring for 5 h, then cooled to rt. A solution of 2 N NaOH (10 mL) was added and the mixture was extracted with ether (3 x 15 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was then purified by flash chromatography on silica gel (40% Ethyl acetate/hexanes) to afford the 68 mg (95%) of the title compound as... 

The unusual 244 was obtained (no yield given) from the cyclization of the sulfonimidamide 243 in ethyl acetate/hexane 1/20 at 60°C. This compound appears to be very stable both in acidic and in basic solution (99BMC (9)1527). 

Then, 1-(3-acetylthio-2-methylpropanoyl)-L-proline is produced. The 1-(3-acetylthio-3-methyl-propanoyl)-L-proline tert-butyl ester (7.8 g) is dissolved in a mixture of anisole (55 ml) and trifluoroacetic acid (110 ml). After one hour storage at room temperature the solvent Is removed in vacuo and the residue is precipitated several times from ether-hexane. The residue (6.8 g) is dissolved in acetonitrile (40 ml) and dicyclohexylamine (4.5 ml) is added. The crystalline salt is boiled with fresh acetonitrile (100 ml), chilled to room temperature and filtered, yield 3 g, MP 187°C to 188°C. This material is recrystallized from isopropanol [ttlo -67° (C 1.4, EtOH). The crystalline dicyclohexylamine salt is suspended in a mixture of 5% aqueous potassium bisulfate and ethyl acetate. The organic phase is washed with water and concentrated to dryness. The residue is crystallized from ethyl acetate-hexane to yield the 1-(3-acetylthio-2-D-methylpropanoyl-L-proline, MP83°Cto 85°C. 

Finally,Captopril is produced. Thethioester (0.85g) isdissolved in5.5N methanolicammonia and the solution is kept at room temperature for 2 hours. The solvent is removed in vacuo and the residue Is dissolved in water, applied to an ion exchange column on the H cycle (Dowex 50, analytical grade) and eluted with water. The fractions that give positive thiol reaction are pooled and freeze dried. The residue Is crystallized from ethyl acetate-hexane, yield 0.3 g. The 1 -(3-mercapto-2-D-methylpropanoyl)-L-proline has a melting point of 103°C to 104°C. 

The reaction is quenched by the addition of 1.28 g (2.94 mmol) of molybdenum pentoxidc/pyridinc/UMPA, and the yellow slurry is stirred initially at OX (30 min), then for 45 min at 25 X. The mixture is added to 1 N sodium hydroxide and extracted with diethyl ether. The ethereal solution is washed with brine, dried over Na,S04 and concentrated in vacuo to give 0.705 g (100%) of an oily, light-yellow solid. Analysis of the crude aldol adduct by 1 C NMR and analytical HPLO (Waters, Radial Pak, 8 mm x 10 cm, silica gel, ethyl acetate/hexane, 15 85) indicates only one. un-diastereomer (2X3S ) accompanied by approximately 10% of the two [Pg.463]

A solution of 0.9 mmol of the imine and l.2mmol of diethyl pyrocarbonate in 1.5 mL of dry ethanol (distilled from magnesium ethoxide) is stirred under nitrogen at 60 C for 24 h. Then the solvent is removed in vacuo and the residue flash chromatographed (silica gel, ethyl acetate/hexane 1 5) to give the product as an oil. 

Removal of the solvent under reduced pressure affords 1.9-2.1 g. of the crude yellow adduct (Note 4). This crude material is dissolved in 8 ml. of hot dibutyl ether (70-80°) and rapidly percolated through approximately 2.0 g. of Plorisil (Note 5). Cooling and then filtering the eluent affords 1.2-1.3 g. (40-44%) of yellow crystals, m.p. 77-80°. An additional recrystallization from dibutyl ether or ethyl acetate-hexane affords pale yellow crystals, m.p. 78.5-80° (Note 6). 

The course of the reaction was followed by TLC (silica gel 60 A, 2.5 x 7.5 cm plates, elution with 95 5 ethyl acetate/hexane, visualization with 50% sulfuric acid followed by heating) by monitoring the disappearance of benzenesulfenate starting material 1. 

Water at 25 C Organic solvents at 20 C Dichloromethane Ethanol Ethyl acetate Hexane Toluene Acetone Benzene... 

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