Solids recrystallization

A-Homo-estra-, 4, )-triene-3, l-dione (50). A solution of bromo ketone (49 0.2 g), silver perchlorate (0.5 g) and 20% aqueous acetone (30 ml) is heated at reflux with stirring for 30 min and then allowed to cool to room temperature. The mixture is filtered to remove precipitated silver bromide (ca. 0.19 g) and the filtrate is diluted with water (200 ml) and then extracted with chloroform. The chloroform extracts are washed, successively with water, 5% sodium bicarbonate solution, water and saturated salt solution. After being dried over anhydrous magnesium sulfate, the solvents are removed at reduced pressure to give a solid. Recrystallization from ethyl acetate gives A-homo-estra-l,4,5(10)-triene-3,17-dione (50 0.17 g) mp 193-197°. 

B g (0 mol) of p-eminophenol hydrochloride is dissolved in 500 cc of water and added to 99 g (0.5 mol) of 4,7-dichloroquinoline. After a few minutes of warming in a steam bath, 4-(4 -hydroxyanilino)-7-chloroquinoline hydrochloride, of sufficient purity for use in further experiments, precipitates as a yellow crystalline solid. Recrystallized from methanol, the MP Is over 300. ... 

Mix together 4.4 grams of ammonium chloride, 18 ml of methanol, 9 ml of water and 3.0 grams of 2-sulfamyl-4-chloro-nitrobenzene. Heat the mixture to reflux. Add portionwise 4.4 grams of iron filings during a period of about VA hours. Cool the mixture and filter. Concentrate the filtrate to a residue. Triturate the residue with 15 ml of water and filter the solid. Recrystallize the solid from aqueous methanol to yield substantially pure 2-sul-famyl-4-chloroaniline. 

Heat a mixture of 6 grams of 2-sulfamyl-4-chloroaniline and 15 ml of ethyl orthoacetate at 100°-110°C for 1.5 hours. Cool and filter the solids. Recrystallize from aqueous ethanol yielding 3-methyl-7-chloro-1,2,4-ben2othiadiazine-1,1-dioxide. This substance is a white crystalline solid melting at 330°C. 

The above obtained CIICI, filtrate is evaporated and the residue is purified by p.l.c. on silica gel with CHClpFtOAc (1 1) to give a white solid. Recrystallization (CHCl3/light pet. ether) gives the m-alcohol 6 yield 0 804 g (51 %) mp 200-202 C d r. (cis/trans) 70 30. 

Di-2-thienyl ditelluride (typicalprocedure) n-Butyllithium (ll.OmL, 2.2 M, 24.2 mmol) is added to an ice-cooled stirred solution of thiophene (2.0 g, 23.8 mmol) in dry THF (50 mL). After 10 min at 0°C and 50 min at room temperature, elemental Te (2.9 g, 22.7 mmol) is added rapidly. All Te is completely dissolved after 30 min, when the yellowish solution is poured into a beaker containing H2O (300 mL). CH2CI2 (200 mL) is then added and air passed through the two-phase system for 1 h. To effect complete oxidation, the beaker is left overnight in the open air. The organic phase is separated and the aqueous phase extracted several times with CHjClj. The combined organic extracts are dried (CaCy and evaporated to give a red solid. Recrystallization from EtOH affords 3.54 g (74%) of di-2-thienyl ditelluride (m.p. 89-90°C). 

The reaction mixture is diluted with an equal volume of water and ex"fcra,cted with a 400-ml. and a 200-ml. portion of methylene chl oride. The combined methylene chloride extracts are washed -with three 250-ml. portions of aqueous 20% sodium chlori e, dried over anhydrous magnesium sulfate, and concentrated to leave a yellow solid. Recrystallization from acetone gives 8.0-9.3 g. (55-64%) of crystalline a-diazo ketone, m.p. 200-202 dec. (Note 10). 

B. 1,3-Dimethyl-6H-benzo[b]naphtho[1,2-d]pyran-6-one (4). Under an argon atmosphere, a 250-mL, oven-dried, round-bottomed flask, equipped with a reflux condenser, is charged with freshly distilled N,N-dimethylacetamide (DMA, 130 mL), 3,5-dimethylphenyl 1-bromo-2-naphthoate (3, 3.24 g, 9.12 mmol), palladium(ll) acetate (205 mg, 0.913 mmol), triphenylphosphine (481 mg, 1.83 mmol), and sodium acetate (1.50 g, 18.3 mmol) (Notes 4 and 5). The orange suspension is degassed three times, placed in a preheated (130°C) oil bath (Note 5), and stirred at 130°C for 12 hr (Note 6). Removal of the solvent at 40°C (0.1 mbar, 0.075 mm) gives a black oily residue, which is Chromatographed (5 x 40 cm column, silica gel 0.063 - 0.2 mm, 170 g, 1 cm of charcoal at the top of the column eluent hexane / diethyl ether 5 1), to yield 2.00 g (80%) of the lactone 4 as a slightly yellow solid. Recrystallization from diethyl ether / hexane delivers 1.63 g (65%) of colorless or pale yellow crystals (Note 7). 

The hexafluoroacetone-protected amino acid 188189 (10 mmol) was dissolved in anhyd MeOH (15 mL) and stirred at rt for 24 h. After additional refluxing for 1 h, the product was precipitated with Et20 and the solid recrystallized (H20, hot H20, MeOH, or EtOH) average yields 50%. 

To a solution of 298 gm (8 equivalents) of hydrazine in ether is slowly added with stirring and cooIing215 gm (1.15 moles) of 3,4-dichlorophenyl isocyanate in 2 liters of ether while keeping the temperature at 20°C. After the addition the ether layer is decanted from the oily layer. On dilution of the oily layer with water is obtained 237.5 gm of a solid. Recrystallization from ethanol and filtration to remove the insoluble l,6-bis(3,4-dichlorophenyl)biurea afford 108.6 gm of a solid, m.p. 175°-177°C. An additional recrystallization from 700 ml of ethyl acetate affords 77.3 gm (30%), m.p. 173°175°C, ir 3.00, 3.10 p. (NH), 5.90 jji (C=0). 

Trimethoxyphenyl)cyclobutanone oxime (0.47 g, 1.87 mmol) in anhyd EtOH (50 mL) containing CHClj (1 mL) and Pt02 catalyst (50 mg) was shaken under H2 (3 atm) in a Parr apparatus for 12 h. The catalyst was removed by filtration through a Celite pad. Concentration under reduced pressure yielded a white solid. Recrystallization (EtOH/Et20) gave the pure amine salt yield 320 mg (66%) mp 219-220CC. 

A solution of this product (7.80 g) and 0.2 mL of 25% NaOMe-MeOH solution in 35 mL of MeOH-THF (6 1) was stirred until the reaction was completed. The mixture was cautiously neutralized with Amberlite IR-120 (H+) ion-exchange resin. After filtration and concentration, the desired product was obtained in quantitative yield as a white solid. Recrystallization in EtOH gave the title componnd as white crystals mp 168°C, [a]D -15.8° (c 0.6, MeOH). 

Confirmation of the bridging behavior of dppm in rhenium dimer chemistry has been obtained by x-ray analysis of the minor product of the reaction of dppm with Re2Cll in acetone (111). The brown, air-stable solid recrystallized from toluene and having the stoichiometry Re2 Gs (dppm)j 2C6H5CH3 has the eclipsed structure with two bridging dppm ligands and one terminal chloride as shown in Fig. 17. This dimer thus differs from the Re2Cls... 

D. (+)-(1S,2R)-trans-2-Phenylcyclohexanol. A 500-mL, round-bottomed flask is charged with a mixture of 52.0 g (0.206 mol) of (+)-(1S,2R)-trans-2-phenylcyclohexyl chloroacetate, 250 mL of 2 N sodium hydroxide, and 100 mL of methanol and then stirred at reflux for 3 hr. TLC analysis (Note 24) indicates complete reaction. The mixture is cooled to room temperature, adjusted to pH 7 with -35 mL of 3 N sulfuric acid and poured into 500 mL of water. The mixture is extracted with two 150-mL portions of dichloromethane and the organic layer is dried over anhydrous sodium sulfate and concentrated on a rotary evaporator (35°C) to afford 37.0 g of a colorless solid. Recrystallization from 100 mL of petroleum elher (30-60°C) at -20°C gives in... 

A solution of 2.1 g 2,5-dimethoxy-4-(methylthio)benzaldehyde in 7,5 mL nitromethane was treated with 0.45 g anhydrous ammonium acetate and held at steam bath temperature for 6 h. The deep red solution was stripped of solvent to give a residue that spontaneously crystallized. This was ground up under 12 mL MeOH, filtered, and washed with MeOH to yield, after air-drying, 1.7 g of 2,5-dimethoxy-4-methylthio-B-nitrostyrene as orange solids. Recrystallization from EtOHprovided rust-orange colored crystals with a mp of 165.5-166 °C. Anal. (C,, H13N04S) C,H,N S calcd, 12.56 found, 11.96. 

The thioureido-acetamide lb (2.00 mmol) and 2 (2.00 mmol) were weighed into a 10-mL ball-mill vessel. The mixture became immediately solid and was ball-milled at 25 Hz for 1 h. 3b remained insoluble in hot ethyl acetate whereas 4b dissolved and was separated by filtration. 3b was recrystallized from DMSO (3b, yield 54%). The ethyl acetate extract was evaporated to dryness and the crude solid recrystallized from ethanol (4b, yield 26%). 

A crystalline film of 314 mg (0.744 mmol) of 1,1,3,3-tctraphcnyl-5,5-dicyano-1,4-pentadiene la, deposited by slow evaporation of a 20% ether in hexane solution, was irradiated at 78 °C for 2.5 h through Pyrex. The resulting orange-red solid was subjected to preparative HPLC eluted with 8% ether and 0.5% acetonitrile in hexane to give 227.1 mg (72.3%) of starting diene and 74.8 mg (23.8%) of 2a as a pale purple-red solid. Recrystallization from ether-hexane yielded 69.7 mg (21.6%) of 2a as a white solid (mp 125-128 °C). 

A solution of l-amino-3-[4-(4-methyl-l-piperazinyl)butyl]-2,4-imidazolidinedione hydrochloride (0.0094 mole), dimethylformamide (75 ml) and 5-(4-chlorophenyl)-2-furancarboxaldehyde [prepared as described in U.S. Patent No. 20 4,882,354, to Huang et al., assigned to Norwich Eaton Pharmaceuticals, Inc., issued November 21, 1984 see Cols. 7 and 8] (1.94 g, 0.0094 mole) is stirred at room temperature for 72 h. The mixture is filtered, collecting the solid. Recrystallization from absolute ethanol/H20 and air-drying gives 2.63 g (0.0050 mole) of l-[[[5-(4-chlorophenyl)-2-furanyl]methylene]amino]3-[4-(4-methyl-l-piperazinyl)butyl]-2,4-imidazolidinedion hydrochloride. 

To a suspension of the ester (3) (0.058 g, 0.16 mmol) in 75% aqueous methanol (2 mL) was added one pellet of potassium hydroxide (0.1 g). The mixture was stirred at 70°C for 1 h during which time the material dissolved. The solution was cooled to room temperature, acidified with 1 N aqueous hydrochloric acid and then extracted with 80% ethyl acetate/hexane. The combined organic layers were dried over anhydrous MgS04, filtered and concentrated to afford a white solid. Recrystallization from dichloromethane/hexane afforded the desired acid (4) as a white, crystalline solid (42 mg, 91%) melting point 230°-231°C. The structure of the product was also confirmed using IR, iH NMR and mass spectroscopy. 

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. 

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