Isopropyl ether recrystallization from

Isodurylyl chloride, 21, 77 (ZZ-ISOLEUCINE, 21, 60 Isonitrosopropiophenone, 23, 1 Isopropyl ether, recrystallization from, 22, 2... 

Sodium hydride (9.3 g, 0.22 mol) was washed with petroleum ether and DMSO (200 ml) was added and the mixture was heated to 100°C. A solution of diethyl malonate (35.2 g, 0.22mol) in DMSO (50 ml) was then added and stirred for 10 min to give a clear solution. A solution of 4-bromo-3-nitrobenzophenone (30.6 g, 0.10 mol) in DMSO (100 ml) was added and the resulting dark solution kept at 100 C for 1 h. The solution was poured into water (3 1) and extracted (2x) with ether. The extract was washed with water, dried (NajSOj and concentrated in vacuo to give an oil which crystallized. The solid was recrystallized from isopropyl alcohol to give 35.4 g (92% yield) of the product. 

Methylsulfinyl -pentyl ketone is prepared by the reaction of the reagent (0.1 mole) and 7.2 g (0.05 mole) of ethyl caproate yielding the crude product as a pasty crystalline mass. The material is dissolved in hot isopropyl ether (20 ml), petroleum ether (30 ml) is added, and the solution cooled to -15°. Filtration yields approx. 6 g of white plates, mp 40-44°. Recrystallization from isopropyl ether affords pure product, mp 45-47°. 

Methylsulfinyl cyclohexyl ketone is prepared by reaction of the reagent (0.08 mole) with 6.24 g (0.04 mole) of ethyl cyclohexanecarboxylate yielding about 7 g of product, mp 62-63° after recrystallization from isopropyl ether. 

Preparation of 4-aza-S-(N-methyl-4-piperidyll-10,11-dihydro-SH-dibenzo[a,d]cycloheptene-S-ol Add 17.4 g of N-methyl-4-chloropiperidine to a stirred mixture containing 3.2 g of magnesium, 20 ml of anhydrous tetrahydrofuran, 1 ml of ethyl bromide and a crystal of iodine. Reflux for two hours, cool to 30°-35°C and add a solution of 13 g of 4-aza-10,11 -dihydro-5H-dibenzo[a,d] cycloheptene-5-one in 25 ml of tetrahydrofuran. Stir for five hours, remove the solvent by distillation in vacuo and add 250 ml of ether. Add 100 ml of 10% ammonium chloride solution and extract the mixture with chloroform. Concentrate the chloroform solution to a residue and recrystallize from isopropyl ether obtaining 20 g of the carbinol,... 

A solution of 1-piperazino ethyl acetate (Q2 mol) in benzene (300 ml) is treated with 3,4.5-trimethoxy cinnamoyl chloride (0,2 mol) in the presence of sodium bicarbonate (0.3 mol). After contacting for one hour at room temperature, the mixture is refluxed for a further hour. The benzene solution is then treated with an aqueous solution of sodium bicarbonate. After evaporation of the solvent, a solid product is obtained which is recrystallized from isopropyl ether. Melting point = 96°C. This base, when treated with hydrochloric acid, gives a hydrochloride having a melting point of 200°C with decomposition. By the action of malaic acid the acid maleate is obtained, having a melting point of 130°C. 

To a well stirred suspension of 9 g of sodium phenyl acetate and 2.4 g of magnesium turnings in 25 cc of anhydrous ether, a solution of 9.4 cc of isopropyl bromide in 50 cc of anhydrous ether are added. The mixture is refluxed for one hour (during which time propane is evolved) and then 5 cc of cyclopentanone in 25 cc of anhydrous ether are added dropwise. The mixture is then refluxed for one hour and poured over ice water containing some hydrochloric acid. The ether solution is separated and extracted with 200 cc of 5% sodium hydroxide. The alkaline solution on acidification gives the free acid which is filtered off, dried in a desiccator and recrystallized from a mixture of ethylene dichloride and petroleum ether. 

After drying over sodium sulfate and concentration to vacuum the remaining residue is subjected to chromatography over silica gel. Using a benzene-ethyl acetate mixture (19 1) there is eluated 900 mg of 6-chloro-1,2a-methylene-A -pregnadiene-17o-ol-3,20-dione-17-acetate, which upon recrystallization from isopropyl ether melts at 200° to 201°C. 

The residue is the 3-N-bis((3-chloroethyl)carbamate of estradiol. The compound melts at 101° to 103°C after recrystallization from isopropyl ether plus hexane (1 1). 

A solution of 69g of sodium in 1,380 ccof absolute alcohol is mixed with 257.4 g of /3-methyl-thioethyl-d -methyl)-n-butvl-cyano-acetic acid ethyl ester and 114 g of thiourea and the whole mass boiled under reflux with stirring for six hours. After concentration under vacuum the residue is taken up in 1.5 liters of water and shaken up thrice, each time with 300 cc of ether. The aqueous alcoholic layer is stripped, under vacuum, of the dissolved ether and mixed with 300 cc of 30% acetic acid under stirring and ice cooling. The precipitated material is sucked off, washed with water, dried and recrystallized from isopropyl alcohol. The thus obtained j3-methvl-thioethyl-(1 -methyD-n-butyl-cyano-ecetyl thiourea forms yellowish green crystals having a melting point of 229°C to 230°C. 

The hydrochloride salt was formed in a mixture of 1 10 isopropyl alcohol diisopropyl ether and recrystallized from acetonitrile, yield 87%, MP 124°C to 125°C. 

The methyl benzoate thus formed is eliminated by steam distillation, and 2.140 g of crude product are obtained, which are dissolved in 20 cc of methylene chloride. This solution is passed through 10 parts of magnesium silicate, elution being performed with 250 cc of methylene chloride containing 5% of acetone. After evaporation of the solvent 2.050 g of product is recovered, which is recrystallized from isopropyl ether. 

To 9 g of n-butyllithium in 200 ml of dry ether 20 g of 3-bromopyridine Is added as quickly as possible at -40°C without raising the temperature. When the addition Is finished the mixture is stirred for another 30 minutes. Thereafter 32.5 g of 0>dimethylamino-4 -bromopro-piophenone is added in such a way that the temperature does not exceed -40°C. The cooling is discontinued and the mixture is stirred during the night whereupon the reaction mixture is poured onto ice and diluted HCI, which is washed with ether and is extracted with 20 ml of methylene dichloride. The methylene dichloride is dried and evaporated. The crystals are dissolved in water, which then is made alkaline with a solution of Na2C03, is extracted with ether, dried, and evaporated and recrystallized from isopropyl ether, petroleum ether 1 1. Yield 4 g of 1 -(4 -bromophenyl)-3-(N,N-dimethylamino)-1 -(3"-pyridyl)-propanol. Melting point 67°C. 

R2 = CH3 (2R,5S)-l-henzoyl-2-lcrt-buty -3,5-dimethyl-4-imida o/idinone yield 85% d.r. 85 15 partial racemization. Enantiomerically pure material is obtained by fractional recrystallization from CH2Cl2/di-ethyl ether at low temperature yield 13% mp 114 117°C [ajj5 —47.7 (c — 1, CHC13)3 R2 = /-Pr (2VL,5S)-l-benzoyl-2-len-butyI-5-isopropyl-3-meth v/-4-itnidazolidinone the product was washed with cold diethyl ether yield 78% d.r. >97 3 partial racemization mp 112°C [a] +24.4 (c = 1.7, CHC13)3... 

A reactor was charged with methyl 6-hydroxy-2-oxohexahydro-3,5-methano-2H-cyclopenta-[b]furan-7-carboxylate (25.0 g) and 2-chloroacetic acid chloride (16.0 g) dissolved in 180 ml of THF and then cooled to below 20°C and treated with the drop-wise addition of pyridine (10.7 g). The solution was stirred at ambient temperature for 1 hour and then combined with 5% aqueous solution of sodium hydrogen carbonate (40 g). Following an ordinary posttreatment workup, 31.5 g of product were isolated after recrystallization from isopropyl ether. 

The freezing point given was determined by the checkers as the temperature of a solid-melt equilibrium for a sample of 99.8% purity. The submitter reports the melting point at 15.3° after recrystallization from isopropyl ether and redistillation. 

Another application of HNLs can be found in the chemoenzymatic synthesis of the broadband antibiotic thiamphenicol and its fluorinated derivative florfenicol [203]. The conversion of 4-methylsulfanyl-benzaldehyde to the mandelonitrile was catalyzed by a novel enzyme from a Chinese almond (Prunus communis L. var. dulcis Borkh). A concentrated powder from the kernels was prepared and a mixture of the cmde meal, aldehyde, and HCN was stirred in isopropyl ether at room temperature for 12 h, yielding the cyanohydrin with 99% ee after recrystallization. The building block formed was then successfully applied in the total synthesis of thiamphenicol and florfenicol (Fig. 41). 

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