Anhydrous toluene

To a suspension containing 4.86 parts of 4-methylbenzenesulfonyl urethane (MP 80° to 82°C) and 36 parts of anhydrous toluene there are rapidly added 2.5 parts of N-amino-3-azabicyclo(3.3.0)octane (BP/18 mm = 86°C). The reaction mixture is heated under reflux for 1 hour. The resulting ciear solution crystallizes on cooling. The crystals are filtered, washed with 2 parts of toluene, then recrystallized from anhydrous ethanol. There are obtained 3.8 parts of the desired product, MP 180° to 182°C. 

A solution of 5-(3-toluene-p-sulfonvloxvpropvl)dibenzazepine (9.2 g) and 1-(2-hvdroxy-ethyDpiperazine (8.6 g) in anhydrous toluene (50 cc) is heated at boiling point under reflux for 4 hours. 

A mixture containing 186 g (0.20 mol) of 2-aminopyridine, 0.55 g of lithium amide and 75 cc of anhydrous toluene was refluxed for 1.5 hours. Styrene oxide (12.0 g = 0.10 mol) was then added to the reaction mixture with stirring over a period of ten minutes. The reaction mixture was stirred and refluxed for an additional 3.5 hours. A crystalline precipitate was formed during the reaction which was removed by filtration, MP 170°C to 171°C, 1.5 g. The filtrate was concentrated to dryness and a dark residue remained which was crystallized from anhydrous ether yield 6.0 g. Upon recrystallization of the crude solid from 30 cc of isopropyl alcohol, 2.0 g of a light yellow solid was isolated MP 170°C to 171°C. 

To a simultaneously stirred and refluxed suspension of 5.6 parts by weight of sodamide in 60 parts by volume of anhydrous toluene, there is added dropwise a solution of 18.4 parts by weight of N-(2-pyridylmethyl)aniline in 20 parts by volume of anhydrous toluene. After the addition is complete, the mixture is refluxed for two hours under constant stirring. 

To the resulting mixture there is added dropwise a solution of 14.9 parts by weight of 2-pi-peridinoethyl chloride in 20 parts by volume of anhydrous toluene and the whole mixture is stirred and refluxed for another two hours. After cooling, water is added carefully to decompose the unreacted sodamide, the separated toluene layer is dried over anhydrous sodium sulfate and the solvent removed under reduced pressure. 

To a mixture of 4.1 parts of 4-piperidinopiperidine-4-carboxamide, 6.4 parts of sodium carbonate, and a few crystals of potassium iodide in 100 parts of anhydrous toluene is added drop-wise a solution of 5.6 parts of 7-chloro-4-fluorobutyrophenone and 40 parts of anhydrous toluene at a temperature of 30°C to 40°C. The mixture is stirred and refluxed for 48 hours. The reaction mixture is cooled and divided between 50 parts of water and 60 parts of chloroform. The combined organic layers-toluene and chloroform-are dried over potassium carbonate, filtered, and evaporated. The oily residue solidifies on treatment with 80 parts of ether. After cooling for 30 minutes at 0°C, there is obtained 1 -[7-(4-fluorobenzoyl)propyl] -4-pi-peridinopiperidine-4-carboxamide melting at about 1 24.5°C to 126°C. 

A mixture of 84 parts of 3,3-diphenyl-3-cyanopropyl bromide, 41 parts of 4-piperidino4-pi-peridinecarboxamide, 64 parts of sodium carbonate, a small amount of potassium iodide and 1,200 parts of anhydrous toluene was stirred, and heated under reflux for 48 hours. At the end of this time the reaction mixture was allowed to cool to room temperature, and 500 parts of water were added. The resultant precipitate was removed by filtration, and triturated with diisopropyl ether. The crystalline material thus obtained was removed by filtration, and re-crystalli2ed from 320 parts of acetone, to give 1 -(3,3-diphenyl-3-cyanopropyl)4-piperidino-4-piperidinecarboxamide, melting at about 149°C to 150°C. 

Stage A Preparation of 17P-BenzoyloxyEstra-4,9,11-Trien-3-one — 0.400 g of 17/3-benzoyl-oxy-4,5-seco-estra-9,11 -diene-3,5-dione is dissolved in 4 cc of toluene under an inert atmosphere. The solution is cooled to 3°C, then 0.4Bcc is added of the solution of sodium tert-amyl-ate in anhydrous toluene, diluted by the addition of a further 4.8 cc of anhydrous toluene. 

Synthesis of N,N -bis(p-carbomethoxybenzoyl) butanediamine (T4T-dimethyl). Dimethyl terephthalate (DMT) (275 g, 1.42 mol) is dissolved at 65°C in a mixture of 1100 mL anhydrous toluene and 85 mL anhydrous methanol in a 2-L flask equipped with a stirrer, condenser, calcium chloride tube, and nitrogen inlet. When all the DMT is dissolved, 15 mL lithium methoxide (1.25 M) is added. 1,4-Butanediamine (BDA) (34 mL, 0.34 mol), dissolved in 150 mL anhydrous toluene and 10 mL anhydrous methanol, is added dropwise in 4-6 h while the nitrogen flow is stopped. Three hours after the start of the BDA addition, the temperature is gradually increased up to 90°C (5°C/h) while the methanol is stripped off. After a total reaction time of 24 h the reaction is stopped. The white... 

Chloroform, HPLC grade Ethyl acetate, HPLC grade n-Hexane, HPLC grade Methanol, HPLC grade Sodium hydroxide Sodium sulfate, anhydrous Toluene, HPLC grade Water, HPLC grade... 

Preparation of Grafted Amine-Functionalized Silica. Silica was pressed, cmshed, and sieved to 40-60 mesh particles and calcined at 550°C overnight. To anhydrous toluene (40 mL), silica (1.0 g) was added under N2 and stirred for an hour. Aminopropyltriethoxysilane (APS 1.0 g, 5.58 mmol) was syringed into mixture and stirred for 24 hours at room temperature under nitrogen. The functionalized silica was then filtered, washed with toluene three times, and dried under vacuum at 50°C. 

Silica Alkylation. To tetiamethyldisihzane (TMDS, 1.0 g) in anhydrous toluene (30 mL), amine-functionalized silica was added and stirred overnight at room temperature under N2. Then it was then filtered, washed with toluene three times, and dried under vacuum at 50°C. Ethanol (190 mL) and nanopure water (10 mL) were mixed, and the pH was adjusted to 4.7 with acetic acid. Isobutyltrimethoxysilane (4.0 mL) was added to the solution, stirred for five minutes, and the modified silica was added. After 10 minutes, the solution was decanted, the... 

General Considerations. The following chemicals were commercially available and used as received 3,3,3-Triphenylpropionic acid (Acros), 1.0 M LiAlH4 in tetrahydrofuran (THF) (Aldrich), pyridinium dichromate (Acros), 2,6 di-tert-butylpyridine (Acros), dichlorodimethylsilane (Acros), tetraethyl orthosilicate (Aldrich), 3-aminopropyltrimethoxy silane (Aldrich), hexamethyldisilazane (Aldrich), tetrakis (diethylamino) titanium (Aldrich), trimethyl silyl chloride (Aldrich), terephthaloyl chloride (Acros), anhydrous toluene (Acros), and n-butyllithium in hexanes (Aldrich). Anhydrous ether, anhydrous THF, anhydrous dichloromethane, and anhydrous hexanes were obtained from a packed bed solvent purification system utilizing columns of copper oxide catalyst and alumina (ether, hexanes) or dual alumina columns (tetrahydrofuran, dichloromethane) (9). Tetramethylcyclopentadiene (Aldrich) was distilled over sodium metal prior to use. p-Aminophenyltrimethoxysilane (Gelest) was purified by recrystallization from methanol. Anhydrous methanol (Acros) was... 

Synthesis of SBA-15 Functionalized with Patterning Agent (2). Patterning agent la (0.5 g/1.12 mmol) was added to 2 g of SBA-15 with anhydrous toluene and... 

Silanol Capping Reaction (3). The synthesis of 3 was carried out by contacting a large excess of hexamethyldisilazane with 2 in anhydrous toluene at room temperature under argon for 24 h. The resulting solid was filtered and washed with toluene and hexanes in a drybox, dried under vacuum at room temperature overnight, and then stored in a drybox. 

The synthesis of (V-heterocyclic isothiocyanates has been a difficult challenge due to their propensity to oligomerize by autocatalysis. In an attempt to alleviate this issue, silver thiocyanate was used in a novel synthesis of 4-quinolyl isothiocyantes <06TL2161>. Reaction of 4-chloroquinoline with silver thiocyanate in refluxing anhydrous toluene for 12 h results in the desired product in quantitative yields and excellent purity. 

In a fume hood, dissolve ICPTES in anhydrous toluene at a concentration of 5 percent (v/v) and also containing 1 percent DIPEA base. 

The immobilized carbamates (40 pmol) were transferred to a sealable 96-well Weflon plate, and admixed with 10 pmol each of various primary or secondary amines dissolved in 400 iL of anhydrous toluene. After sealing, the plate was irradiated in a multimode microwave instrument, first generating a ramp to reach 130 °C within 45 min and then holding this temperature for an additional 15 min. After cooling, the resins were filtered with the aid of a liquid handler and the filtrates were concentrated to obtain the desired substituted ureas in good purity and reasonable yields. Anilines reacted rather sluggishly and 2-substituted benzyl carbamates afforded somewhat inferior results. 

In the dry flask was dissolved (1S, 2 S)-A-methy lpseudoephedrine (430 mg) in anhydrous toluene (10 mL) under argon. The reaction mixture was placed in a cooling bath equipped with a contact thermometer stirred and cooled to 0 °C. Diethylzinc (1 mL) was added carefully via a syringe (evolution of ethane). 

The bath was cooled to —78 °C and a solution of 2-uobutylidene-1 -tetralone (200 mg) in anhydrous toluene (2mL) was added via a syringe to the cold mixture. The reaction mixture was stirred at this temperature for 30 minutes... 

The flask was filled with the catalyst (50 mg) and anhydrous toluene (4 mL). The mixture was refluxed until 3.5 mL of solvent was recovered. The catalyst was azeotroped twice with toluene (4 mL) and then cooled to room temperature under argon. 

The Dean and Stark apparatus was removed, replaced by a condenser (the solution was flushed continuously with nitrogen) and the catalyst dissolved in anhydrous toluene (2 mL). Borane-dimethylsulfide (0.5 mL of a 2 M solution in tetrahydrofuran) was added to the mixture, which was heated to 110 °C. 

The adipoylated film was washed several times with anhydrous toluene and dioxane, followed by reaction with 7-hydroxycoumarin in dioxane containing sodium hydride for 2 hrs at room temperature. After coupling the coumarin, the film was extracted with methanol in a Soxhlet apparatus, rinsed with water, and dried under vacuum... 

S,5R)-1 -ethynyl-3,5-dihydroxy-2-methyl-l-cyclohexene (0.8215 mmol) anhydrous toluene (30 mL) dichloromethane ethyl acetate hexanes... 

An alternative approach to N-S bond formation involves the aza-Wittig-type reaction of sulfoxides (Scheme 26) <2004SL101>. Initial Staudinger ligation of aryl azide 195 with triphenylphosphine afforded iminophosphorane 196, which was purified by column chromatography and then heated in anhydrous toluene, producing benzothiazines 62 and 197. The N-S bond was found to be rather sensitive to hydrolysis and cleavage to 198 was observed upon treatment of benzothiazines 62 or 197 with wet THF. 

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