Hexane 2-phenyl

Phenyl-carboxy-methyien)-tetra-hydro- Vl/3, 608 Hexan 1 -Phenyl-1,3,5-trioxo-VII/2a, 629 Naphthalin... 

TO a solution of 0.10 mol of phenyl acetyl one (commercially available, see also Ref. 1) in 100 ml of dry THF was added a solution of 0.21 mol of butyllithium in about 145 ml of hexane. During this addition the temperature was kept below -20°C. The obtained solution was cooled to -65°C and a solution of 0.12 mol of KO-tert.--CijHg (commercially available, see Chapter IV, Exp. 4, note 2) in 100 ml of THF was added, while keeping the temperature below -55°C. After an additional 15 min the cooling bath was removed, the temperature was allowed to rise to -10°C and was kept at that level for 1 h (note 1). The reddish suspension was subsequently cooled to -50°C and 0.32 mol of trimethylchlorosi1ane was added in 10 min. The cooling bath was then removed and the temperature was allowed to rise to 10°C. 

Phenyl-3-oxopropanoic acid (25 mmol) and EtjN (87.5 mmol) were dissolved in THF (150 ml) and cooled to —40°C. Ethyl chloroformate (27.5 mmol) was added dropwise to this solution and then the reaction mixture was stirred for 30 min at —20°C. Di-n-hexylamine (27.5 mmol) was added to the suspension and it was stirred at room temperature for an additional hour. The reaction mixture was diluted with water (100 ml) and extracted with ether (400 ml). The extract was washed with aq. 5% HCl (100 ml) and brine (2 X 100 ml) and dried over NajSO. The crude amide was obtained by removal of the solvent in vacuo and phenylhydrazine (25 mmol) was added. The mixture was heated to 100°C for 30 min. The residue was held in vacuo to remove the water formed and then powdered ZnCl2 (125 mmol) was added. The mixture was heated at 170"C with manual stirring for 5 min. The cooled residue was dissolved in acetone (100 ml) and diluted with ether (500 ml). Water (100 ml) was added. The organic layer was separated and washed successively with 5% aq. HCl (100 ml) and brine (2 x 100 ml) and dried over NajSO. The solvent was removed in vacuo, and the residue was recrystallized from EtOAc-hexane. The yield was 79%. 

Diphenoxylate Hydrochloride. l-(3-Cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxyhc acidmonohydrochlorhydrate [3810-80-8] (Lomotil) (13) is a white, odorless, crystalline powder that melts at 220—226°C. It is soluble ia methanol, spariagly soluble ia ethanol and acetone, slightly soluble ia water and isopropyl alcohol, freely soluble ia chloroform, and practically iasoluble ia ether and hexane. The method of preparation for diphenoxylate hydrochloride is available (11). Diphenoxylate hydrochloride [3810-80-8] (13) is an antidiarrheal that acts through an opiate receptor. It has effects both on propulsive motility and intestinal secretion. Commercial forms are mixed with atropiae to discourage abuse. 

A solution of 7-chloro-2.3-dlhydro-1-acetyl-S-phenyl-1H-1,4-benzodlazepine-4-oxlde 1 (7 0 g, 22 mmol) in AC20 (60 mL) was relKjxed lor 7 h. The solvent was removed m vacuum arxl the residue was triturated with EtaO. The crystalline product after recrystaillzation from hexane CH2CI2 gave 4.6 g ol 2 (59%), irp ITT-ITg-C. 

Olmethyl-3-methoxy-3-phenyl-l-(2,6-dimethyiphenyi)-lH>lmldazo(l,2 b) pyrrazol-2(3H)-one (3) Phosphorane 2 (t 48 g 3 mmol) and 2 6 dimethylphenylisocya-nate 3 (0 59 g 4 mmol) in PhMe (30 mL) was heated under reflux with stimng for 16 h (TLC EtOAc hexane I 6) Evaporation and column chromatography (silica gel EtOAc/hexane 1 6) afforded crude 4 Recrysiallization from EtaO petroleum ether gave 0 930 g (66%) mp 126 5 130"C... 

A-tert-Butyl a-phenyl nitrone [3376-24-7] M 177.2, m 73-74 . Crystd from hexane. 

Diphenyl disulfide (phenyl disulfide) [882-33-7] M 218.3, m 60.5 . Crystd from MeOH. [Alberti et al. J Am Chem Soc 108 3024 1986]. Crystd repeatedly from hot diethyl ether, then vac dried at 30° over P2O5, fused under nitrogen and re-dried, the whole procedure being repeated, with a final drying under vac for 24h. Also recrystd from hexane/EtOH soln. [Burkey and Griller 7 Am Chem Soc 107 246 1985.]... 

A-Phenyl-2-naphthylamine [135-88-6] M 219.3, m 107.5-108.5°, 110°, pKjs,-0.5. Crystd from EtOH, MeOH, glacial acetic acid or benzene/hexane. 

In the rearrangement of 4,4-diphenylcyclohexenone to 5,6-diphenylbicyclo-[3.1.0]hexan-2-one, there is a strong preference for formation of the endo phenyl... 

Equation (16) was tested against some data obtained for (R) 4-phenyl-2-oxazolidinone using a range of mixtures of ethanol, acetonitrile and -hexane as the mobile phase. The column chosen was similar to that previously used for the separation of the 4-phenyl-2-oxazolidinone which was 25 cm long, 4.6 mm I.D. packed with 5 mm silica particles bonded with the stationary phase Vancomycin. The results obtained are shown in Table 1 and this is the data used in subsequent computer calculations. 

A-Fluoro-2,4,6-tnmethylpyndmium inflate (1 mmol) is added m several portions at room temperature to a tetrahydrofuran solution of sodium diethyl phenyl-malonate, obtained from 1 mmol of diethyl phenyl malonate and sodium hydnde at 0 C in tetrahydrofuran The reaction imxture is poured mto dilute hydrochlonc acid and extracted with ether The ether extract is washed with sodium bicarbonate and water and dned over magnesium sulfate The oily residue obtamed after removal of tihe ether is chromatographed on sihca gel (dichloromethane-hexane, 1 1) to give diethyl fluorophenylmalonate in 83% yield... 

Preparation of cholesta-5,7-diene-ia,3/3-diol a solution of 500 mg of the 1,4-cyclized adduct of cholesta-5,7-dien-3/3-ol-ia,2a-epoxideand 4-phenyl-1,2,4-triazoline-3,5-dione in 40 ml of tetrahydrofuran is added dropwise under agitation to a solution of 600 mg of lithium aluminum hydride in 30 ml of THF. Then, the reaction mixture liquid Is gently refluxed and boiled for 1 hour and cooled, and a saturated aqueous solution of sodium sulfate is added to the reaction mixture to decompose excessive lithium aluminum hydride. The organic solvent layer is separated and dried, and the solvent Is distilled. The residue Is purified by chromatography using a column packed with silica gel. Fractions eluted with ether-hexane (7 3 v/v) are collected, and recrystallization from the methanol gives 400 mg of cholesta-5,7-diene-la, 3/3-diol. 

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... 

Fig. 2-11. The effect of flow rate on the selectivity of a-methyl-a-phenyl succinimide on teicoplanin CSP (250 X 4.6 mm) in normal phase. The mobile phase was ethanol hexane (20/80 v/v) at ambient temperature (23 °C).

A solution of 2-bromo-4-chloro-5-phenyl-2,3-dihydro-1-benzothiepin (1.02 g, 2.84 mmol) in THF (3 mL) was added in one portion to a solution of DBN (0.52 g, 4.2 mmol) in THF (3 mL) at rt. After stirring for 2h, the red mixture, containing some precipitate, was poured into 10% aq HC1 (20 mL) and the aqueous solution was extracted with CHCl, (2x15 mL). The combined extracts were washed with H20, dried (MgS04) and carefully concentrated in vacuo at subambient temperature. The yellow oil, which solidified on cooling, was chromatographed [alumina (Merck 71707,25 g), hexane] to give colorless crystals yield 0.58 g (76%) mp 87-88 °C. 

Phenyl-2-oxa-3-azabicyclo[3.2.0]hepta-3,6-diene (11 0.200 g, 1.17 mmol) in hexane was irradiated in a quartz vessel using a Rayonet photoreactor to give the product as a yellow oil yield 0.160 g (SO %). The compound can be distilled below 100 C at 10 4Torr. It gradually resinifies when kept in air at 20 C. 

BuOK. (15.4 g, 0.139 mol) was added in portions to 6-chloro-2-(chloromethyl)-4-phenyl-l,2-dihydro-quinazoline 3-oxide (11a 42.2 g, 0.137 mol) in THF (700 mL), cooled in acetone/solid carbon dioxide, and the mixture was stirred for 4.5 h as it warmed to 20 C. It was filtered through Celite, the filtrate was evaporated under reduced pressure and the residue was recrystallized (benzene/hexane) to give the crude aziridinoquinazoline oxide 12a yield 22.Og (57%) mp 135-136.5 C. 

A solution of 0.11 mol of 1.5M butyllithium in hexane is added to 30 mL of THF under a layer of argon or nitrogen at —78 C, followed by 0.10 mol of (4S,5/ )-1-allyl-3,4-dimcthyl-5-phenyl-2-imidazolidinone in 75 mL of THF. After 25 min, a solution of 0.11 mol of chlorotris(diethylamino)titanium in 30 mL of THF is introduced. The mixture is stirred at — 20 °C for 45 min, then 0.11 mol of the aldehyde or ketone in 10 mL of THF is added. After 2 h. 20 mL of water and 200 mL of diethyl ether are added. The ethereal solution is separated, washed with 20 mL of 10% aq NaHS03 followed by 20 mL of water, dried over Na2S04 and concentrated, whereupon the product crystallizes. Diastereomerically pure samples are prepared by recrystallization from hexane or hexane/ethyl acetate. 

Conjugate Addition. To a solution of 1.5 mmol of lithium dialkylcuprate at — 25 CC is added 1 mmol of methyl ( )-3-[(25,45,55)-3-benzyloxycarbonyl-4-methyl-5-phenyl-2-oxazolidinyl]-propenoate dissolved in 1 mL of dry diethyl ether. After 30 ntin at — 25 C, the mixture is treated with an aq NH3/NH4C1 pH 8 buffer solution and then stirred at r.t. for 15 min. After diethyl ether extraction, the organic layers are dried over Na,S()4 and filtered and the solvent is evaporated under reduced pressure. The crude products are checked by H- and l3C-NMR analyses in order to determine the diastereomer ratios (g 95 5) and then purified by flash chromatography (hexane/ethyl acetate 80 20) yield 70-72%. 

S, 4oR, 6R S,8aR )-6- ert-hiilyloctahydro-8a-hydroxy-4-phenyl-1H-2-benzothiapyran 2,2-dioxide yield 100% mp 205.5-206.5 °C (benzene/hexane) ... 

Stirring is continued for 2 hours at room temperature, and then methanol is added until a clear solution is obtained (ca. 10 ml. of methanol is required, and some heat is generated). When the solution has cooled, it is washed successively with 200 ml. of aqueous 2N potassium carbonate and 200 ml. of water. The aqueous phases are combined, washed with three 100-ml. portions of chloroform, and discarded. The organic phases are then combined, dried over sodium sulfate, and decolorized with activated carbon. Concentration of the chloroform solution thus obtained provides three crops of pale yellow crystals, which are washed with 30% hexane in chloroform and dried for 2 hours at 80°/0.1 mm. The total yield of 3-(2-phenyl-l,3-dithian-2-yl)indole is 22.3-25.4 g. (72-81%), m.p. 167-169° (Note 7). This material requires no further purification for use in Parts D or E. 

All analytical and test samples were recrystd from either acet-n-hexane mixts or acetonitrile and dried in an Abderhalden drying app over refluxing nitrobenzene for at least 4 hours. The product was identified as 2,2,2,f,4,4/,4, 6,6,6w-nonanitroter-phenyl by elemental analysis and X-ray molecular wt detn ... 

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