1- Chloro-2-ethyl-3-hexane

Medium Boiling Esters. Esterificatioa of ethyl and propyl alcohols, ethylene glycol, and glycerol with various acids, eg, chloro- or bromoacetic, or pymvic, by the use of a third component such as bensene, toluene, hexane, cyclohexane, or carbon tetrachloride to remove the water produced is quite common. Bensene has been used as a co-solvent ia the preparatioa of methyl pymvate from pymvic acid (101). The preparatioa of ethyl lactate is described as an example of the general procedure (102). A mixture of 1 mol 80% lactic acid and 2.3 mol 95% ethyl alcohol is added to a volume of benzene equal to half that of the alcohol (ca 43 mL), and the resulting mixture is refluxed for several hours. When distilled, the overhead condensate separates iato layers. The lower layer is extracted to recover the benzene and alcohol, and the water is discarded. The upper layer is returned to the column for reflux. After all the water is removed from the reaction mixture, the excess of alcohol and benzene is removed by distillation, and the ester is fractionated to isolate the pure ester. 

Chloro-2-hydrazino-4-phenylquinoline A stirred mixture of 2,6-dichloro-4-phenylquino-line 12.7 g,0.01 mol) and hydrazine hydrate (6.8 g) was refluxed under nitrogen for 1 hour and concentrated in vacuo. The residue was suspended in warm water, and the solid was collected by filtration,dried and recrystallized from ethyl acetate-Skelly B hexanes to give 1.81 g (67% yield) of 6[Pg.46]

The mixture of 7.9 g of ethyl a-(4-aminophenyl)propionate and 8.3 g of ethyl 2-chloro-methylbenzoate is refluxed under nitrogen for one hour. The residue is recrystallized from hexane, to yield the ethyl a-[4-(1-oxo-isoindolino)-phenyl]-propionate of the formula... 

To the mixture of 85.5 g ethyl a-(3chloro-4.aminophenyl)-propionate hydrochloride, 142 g sodium carbonate and 600 ml dimethyl formamide, 107 g 1,4room temperature. The mixture is filtered, the filtrate evaporated in vacuo, the residue is triturated with hexane, the mixture filtered, the residue washed with petroleum ether and the filtrate evaporated. The residue is combined with 280 ml 25% aqueous sodium hydroxide and the mixture refluxed for 8 hours. After cooling, it is diluted with water, washed with diethyl ether, the pH adjusted to 5 to 5.2 with hydrochloric acid and extracted with diethyl ether. The extract is dried, filtered, evaporated and the residue crystallized from benzene-hexane, to yield the a-(3-chloro-4-pyrrolinophenyl)-propionic acid melting at 94°C to 96°C. 

Lipases from C. antarctica and P. cepacia showed higher enantioselectivity in the two ionic liquids l-ethyl-3-methylimidazolium tetrafluoroborate and l-butyl-3-methylimidazolium hexafluoroborate than in THE and toluene, in the kinetic resolution of several secondary alcohols [49]. Similarly, with lipases from Pseudomonas species and Alcaligenes species, increased enantioselectivity was observed in the resolution of 1 -phenylethanol in several ionic liquids as compared to methyl tert-butyl ether [50]. Another study has demonstrated that lipase from Candida rugosa is at least 100% more selective in l-butyl-3-methylimidazolium hexafluoroborate and l-octyl-3-nonylimidazolium hexafluorophosphate than in n-hexane, in the resolution of racemic 2-chloro-propanoic acid [51]. 

A gas liquid chromatographic (GLC) method was described for determining residues of Bayer 73 (2-aminoethanol salt of niclosamide) in fish muscle, aquatic invertebrates, mud, and water by analyzing for 2-chloro-4-nitroaniline, a hydrolysis product of Bayer 73 [83]. Residues were extracted with acetone-formic acid (98 + 2), and partitioned from water samples with chloroform. After sample cleanup by solvent and acid base partitioning, the concentrated extract was hydrolyzed with 2N NaOH and H202 for 10 min at 95°C. The 2-chloro-4-nitroaniline was then partitioned hexane ethyl ether (7 + 3) and determined by electron capture GLC. Average recoveries were 88% for fish, 82% for invertebrates, 82% for mud, and 98% for water at 3 or more fortification levels. 

Azatricyclo[2.2.1.02 6]hept-7-yl perchlorate, 2368 f Azetidine, 1255 Benzvalene, 2289 Bicyclo[2.1.0]pent-2-ene, 1856 2-/ert-Butyl-3-phenyloxaziridine, 3406 3 -Chloro-1,3 -diphenyleyclopropene, 3679 l-Chloro-2,3-di(2-thienyl)cyclopropenium perchlorate, 3388 Cyanocyclopropane, 1463 f Cyclopropane, 1197 f Cyclopropyl methyl ether, 1608 2,3 5,6-Dibenzobicyclo[3.3.0]hexane, 3633 3,5 -Dibromo-7-bromomethy lene-7,7a-dihy dro-1,1 -dimethyl-1H-azirino[l,2-a]indole, 3474 2.2 -Di-tert-butyl-3.3 -bioxaziridinc, 3359 Dicyclopropyldiazomethane, 2824 l,4-Dihydrodicyclopropa[ >, g]naphthalene, 3452 iV-Dimethylethyl-3,3-dinitroazetidine, 2848 Dinitrogen pentaoxide, Strained ring heterocycles, 4748 f 1,2-Epoxybutane, 1609 f Ethyl cyclopropanecarboxylate, 2437 2,2 -(l,2-Ethylenebis)3-phenyloxaziridine, 3707 f Methylcyclopropane, 1581 f Methyl cyclopropanecarboxylate, 1917 f Oxetane, 1222... 

The mixture of products was separated by column chromatography on a silica gel column with hexane/ethyl acetate (7 3) as the eluent. (5)-4-Chloro-3-hydroxybutanoate eluted first from the column followed by (5)-4-cyano-3-hydroxybutanoate. 

In one study, various distinct types of polar modifiers to n-hexane were tested for 3-chloro-l-phenylpropanol (3CPP) and 1-phenylpropanol (IPP) enantiomer separation [53]. Thereby, alcohol modifiers turned out to be more effective displacers of the solutes from the adsorption places on the sorbent surface, yet aprotic polar modifiers provided higher separation factors (with ethyl acetate in n-hexane affording the best separations for these chiral alcohols). It is evident, though, that the optimal choice of polar modifier is strongly solute dependent and can therefore not be generalized. 

FIGURE 1.8 Effect of the mole fraction of polar modifier (ethyl acetate) in n-hexane on the reciprocal of the retention factor for the separation of 3-chloro-l-phenylpropanol enantiomers on a 0-9-(terf-butylcarbamoyl)quinidine CSP. Temperature, 22°C. (Reproduced from L. Asnin, and G. Guiochon, J. Chromatogr. A, 1091 11 (2005). With permission.)... 

The mixture was filtered through a pad of Celite (3.0 g), washed with ethyl acetate (20 mL) and concentrated on a rotary evaporator. Silica gel chromatography of the residue (hexane-ethyl acetate, 30 1) gave (7/f)-2-chloro-7-isopropyl-6,7-dUiydro-5//-l-pyrindine (1.14g, 88%) as an oil. 

Medium Boiling Esters. Esterification of ethyl and propyl alcohols, ethylene glycol, and glycerol with various acids, e.g.. chloro- or bromoaceiic. or pyruvic, by the use of a third component such as benzene, toluene, hexane, cyclohexane, or carbon tetrachloride to remove the water produced is quite common. 

A pure sample of diazo ketone can be obtained by chromatography on silica gel using 15% ethyl acetate/hexane as an eluent, Rf = 0.37. The checkers estimate the purity of the crude diazo ketone to be 90-91% based on careful column chromatography of 1 0-g aliquots. They further estimate that approximately 5-6% of 1 -chloro-4-phenyl-2-butanone is also produced in the reaction. The spectral properties of 1-diazo-4-phenyl-2-butanone are as follows 1H NMR (300 MHz, CDCI3) 8 2.59-2.64 (m, 2 H), 2.95 (t, 2 H, J = 7) 5.20 (broad s, 1 H), 7.17-7.31 (m, 5 H). 

Phenyl chlorothionoformate (4.66 g, 27 mM) is added to a mixture of 2-chloro-(3, 5 -0-tetraisopropyldisiloxyl)adenosine (14 g, 25.8 mM), 4-dimethylaminopyridine (DMAP) (6.88 g, 56.4 mM) and acetonitrile (400 mL) at room temperature under nitrogen, and stirred overnight. The solvent is removed in vacuo and the residue is purified by column chromatography on silica gel (200 g) with ethyl acetate/hexane (4 6) to yield the title compound as a pale yellow powder (9.8 g, 56%, MP 153-155°C). NMR, IR and elemental analysis are confirmed the structure of the title compound. 

After about the first 6-8 hours an additional 30 ml of 70% ethyl alcohol may be added. Remove about 50% of the solvent by distillation in vacuo. Add a small amount of ice water and acidify with glacial acetic acid. Extract with chloroform (6-8 times), since the product precipitates from the acetic acid solution as a thick emulsion which cannot be filtered. Concentrate the chloroform extracts to a small volume and precipitate the product with hexane to give crude 8-chloro-6,ll-dihydro-ll-(4-piperidylidene)-5H-benzo[5,6]cyclohepta[l,2-b]pyridine acetic acid salt, m.p. 197-200°C. Recrystallize from benzene-hexane to obtain the product, m.p. 199-200°C. Yield 4.0-4.5 g. 

A solution of 2-(2-amino-5-chlorophenyl)-4-cyclopropyl-l,l,l-trifluoro-3-butyn-2-ol (15.00 g, 0.0518 mol) and 41.98 g (0.259 mol) of 1,1 -carbonyldiimidazole in 250 mL of dry THF was stirred under argon at 55°C for 24 hours. The solvent was removed on a rotary evaporator and the residue was partitioned between 500 mL of ethyl acetate and 400 mL of water. The layers were separated and the aqueous phase was extracted once more with ethyl acetate. The combined ethyl acetate extracts were washed with 2 times 200 mL of 2% aqueous HCI, saturated aqueous NaHC03, and brine. Drying over MgS04, filtration, and removal of the solvent in vacuo provided 16.42 g of the title compound as a solid. Recrystallization from ethyl acetate/hexane afforded 12.97 g of analytically pure ()-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-l,4-dihydro-2H-3,l-benzoxazin-2-one as a white crystals. Melting point 178°-180°C. 

The mother liquors from Step C above were purified by column chromatography on silica gel using 10% ethyl acetate in hexanes as eluant. The pure, undesired diastereomer (a colorless foam) was hydroylzed according to Step D. The enantiomeric benzoxazinone, (+)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-l,4-dihydro-2H-3,l-benzoxazin-2-one, was obtained as white crystals. Melting point 131°-132°C [a]D20 =+84.4° (CHCI3, c=0.005 g/mL). 

Acetoxymethyl-7,8-difluoro-2,3-dihydro-4H-[l,4]benzoxazine (m.p. 73-74°C) was synthesized by hydrogenation of a compound prepared from 2,3-difluoro-6-nitrophenol, l-acetoxy-3-chloro-2-propane and potassium iodide. The hydrogenation was carried out on Raney nickel. The resulting compound was dissolved in THF, and 3,5-dinitrobenzoyl chloride and pyridine were added thereto, followed by heating at 60°C for 3 hours. The mixture was concentrated, and the concentrate was dissolved in ethyl acetate, washed successively with diluted hydrochloric acid, an aqueous solution of sodium bicarbonate and water, dried over anhydrous sodium sulfate and concentrated. Addition of n-hexane to the concentrate caused precipitation of yellow crystals of a racemate. The yield of 3,5-dinitrobenzoyl derivative of the ()-3-acetoxymethyl-7,8-difluoro-2,3-dihydro-4H-[l,4]benzoxazine 3.93 g. 

Bromomethyl-2-cyanobiphenyl (4.6 g) was alkylated onto 2-n-butyl-4-chloro-5-(hydroxymethyl)-imidazole. For separation of the product was used a flash chromatography in 1 1 hexane/ethyl acetate over silica gel. The regioisomeric products yielded 2.53 g of the faster eluting isomer. Recrystallization from acetonitrile yielded 1.57 g of analytically pure 2-n-butyl-4-chloro-l-[2,-cyanobiphenyl-4-yl)methyl]-5-(hydroxymethyl)-imidazole, melting point 153.5 -155.5°C. 

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