Cooling suspension

Uorking up was carried out by adding 35 ml of 36% HCl to the cooled suspension (note 3) and subsequently extracting the mixture 15 times with small 60 ml)... 

Dlcarboxyfuran-2-acetlc acid (3). To a cooled suspension ol sodium sand (17,2 g,... 

Hydroxy-6-cyanoclnnollne (4). A cooled suspension of 3 (1.0 g, 6 1 mmol) in 2N Hi (15 mL) was treated with 15% NaNOa (15 mL) under stirnrvg The mixture was heated on a wa bath for 1 h, cooled, filtered and the crude 4 was dissolved m Na2C03 solution, treated with Nomte charcoal HOAc precipitated 4 Recrysialllzaiion from EtOH attorded 4, mp 284-285°(... 

This thione was obtained in 87% yield by a modification229 in which a stirred cooled suspension of P2S5 (9.3 g, 42 mmol) in THF (170mL) under N2 was treated with 15% BuLi in hexane (50.4ml., 84 mmol) at 5-10 C. The mixture was stirred at 20 C for 1 h when a clear yellow solution resulted. 7-Chloro-5-phcnyl-l 7/-l,4-benzodiazcpin-2(37/)-one (21.64 g, 80 mmol) was added and the mixture was heated under reflux for 16h, cooled and the product was collected. b See ref 230. 

Preparation of Boriozirconocene Complex 16 (Scheme 7.5) [33] To a stirred ice-cooled suspension of the Schwartz reagent (0.26 g, 1 mmol) in dry CH2C12 (1 mL) was added a solution of B-hexenyl-9-BBN 15 (0.20 g, 1 mmol) in dry CH2C12 (1 mL). The resulting cloudy mixture became a dear yellow solution in 1 h at 0 °C (or 10 min at ambient temperature), indicating the formation of 16. 

When nitrous gases (from arsenious oxide and nitric acid, d. 1 -35) are passed into a well-cooled suspension of aniline nitrate in water, and alcohol and ether are then added gradually, crystalline phenyldiazonium nitrate is obtained. At most only 2 g. of aniline are used, and of the diazonium salt only as much as covers well the tip of a knife-blade is dried on porous plate, after collecting at the pump and washing with alcohol-ether (1 1). 

B. DicMoromethylenetriphenylphosphorane. In one jiortion 131 g. (0.5 mole) of triphenylphosphine (Note 7) is added to the cooled suspension of potassium /-butoxide in heptane, and to the well-stirred mixture a solution of 59.5 g. (0.5 mole) of chloroform in 500 ml. of dry heptane is added dropwise over a period of... 

To a cooled suspension (0 C) of 3.07 g (20 mmol) of ( + )-(l.S,2fl)-norephedrinc in 30 mL of diethyl ether are added 3.17 g (24 mmol) of propionic anhydride and 3.4 g of solid NaHCOj in portions at a rate such that the pH of the two-phase system is between 7 and 8. The reaction mixture is stirred at 25 C for 45 min and then extracted with three 50-mL portions of ethyl acetate. The combined extract is washed successively with dilute hydrochloric acid and sat. brine, dried over MgSQ4. and concentrated leaving 3.81 g (90.5%) of crystalline material. Recrystallization (benzene/petroleum ether) uives pure A-(l-oxopropyl)norcphednne mp 107.5 -108.5°C [x] J9 +26.72 (c = 2.62, ethanol). 

N 43.29% wh unstable ndls of lachrymatory smell, mp 32 to 35°. Can be prepd by adding with intensive stirring acryloyl chloride in paraffin oil to ice-cooled suspension of NaNs inparaffin oil stirring is continued until chloride is completely consumed (ca 24 hours), and the filtered soln fractionated in vacuo (8-9 mm) to give crude product, which on redistn yields pure compd. Its expl props were not investigated Refs l)Beil—not found 2)T.Lieser, GerP... 

A solution of methyl 4,6-0-benzylidene-3-chloro-3-deoxy-p-D-allopyranoside [29] (33, 12.6 g) in dry tetrahydrofuran (500 mL) containing sodium benzoate (12 g) was boiled for 2 h under reflux. The cooled suspension was filtered, and the filtrate was evaporated to dryness. The residue was extracted with chloroform, and the extract was washed with water, dried (MgS04), and evaporated to dryness. Crystallization of the product from chloroform-petroleum ether gave methyl 4,6-0-benzylidene-P-D-eryriiro-hex-3-enopyranoside 43, yield 8.8 g (85%), mp 134°-135°C, [ot]D -43° (c 1.58, CHC13). 

Cool suspension under continuous agitation and transfer to a 25-ml volumetric flask. Rinse beaker and stir-bar to ensure quantitative transfer. Bring to volume with water. 

C.) The solid remaining after filtration of the cooled suspension is recrystallized from diethyl ether by cooling the saturated solution to — 70°C. Yield, based upon phosphonitrilic chloride—cyclic trimer, is 80-95 g. (60-72%) m.p., 163-165°C. Anal. Calcd. for N3P3C14 (NH2 )2 N, 22.68 H, 1.31. Found N, 22.94 H, 1.35. The checkers report equally good results, working on one-third of the above scale. 

A solution of N-(4-pyridinyl)-lH-indol-l-amine (6 g) in 25 ml of dimethylformamide was slowly added to an ice-cooled suspension of NaH (1.3 g of 60% NaH dispersion in mineral oil was washed with hexanes, the liquid was decanted and the residual solid was dispersed in 5 ml of dimethylformamide). After anion formation, a solution of 1-bromopropane (4 g) in 5 ml of dimethylformamide was added. After one hour of stirring at ambient temperature, the reaction mixture was stirred with ice-water and extracted with dichloromethane. The organic extract was washed with water and saturated sodium chloride solution, was dried over anhydrous magnesium sulfate, filtered and concentrated to 8 g of oil. This oil was purified by HPLC (silica, ethyl acetate) and thereafter by column chromatography (alumina, ether) to give 6.4 g oil. This oil was converted to the maleate salt and recrystallized from methanol/ether to give 6.8 g of crystals, m.p. 115-116°C. 

To an ice-cooled suspension in distilled water (15 ml) of 7-ethyl-10-[l-(4-piperidino)piperidino]carbonyloxycamptothecin (1.00 g, 1.7 mmol) was added 0.1 N HCI (15.3 ml, 1.53 mmol), and the suspension was stirred vigorously for 5 minutes under cooling in an ice bath and filtered off. 7-Ethyl-10-[4-(l-piperidino)-l-piperidino]carbonyloxycamptothecin hydrochloride was obtained in yield 96%. 

Methylenedioxyphenylacetic acid (18.0 g) was added portion wise over 30 minutes to a stirred, ice-cooled suspension of lithium aluminium hydride (4.0 g) in ether (400 ml) and the mixture was stirred at temperature for two hours, quenched by the cautious addition of saturated aqueous ammonium chloride solution and filtered. The filtrate was washed with 10% aqueous sodium carbonate solution, dried over magnesium sulfate and evaporated to give the title compound as a pale yellow oil (15.01 g, 90%), which was characterized by its tH-NMR spectrum. 

Add silver salt (2 eq) and base (2 eq), protect from light, and cool suspension to -15°C (see Note 3). 

A suspension prepared from 4.25 g. of 95% sodium borohydride (0.11 mole) and 150 ml. of tetrahydrofuran is cooled in an ice-water bath and stirred while a solution containing 17 ml. (0.13 mole) of boron trifluoride-diethylether in 60 ml. of tetrahydrofuran is added dropwise over a period of 45 minutes. Thirty grams (0.11 mole) of triphenylphosphine is dissolved in 130 ml. of tetrahydrofuran, and this solution is added through a dropping funnel to the cooled suspension (1 hour). The mixture is allowed to warm to room temperature. Solids are collected by filtration, and the crude product is recovered by evaporation of the solvent from the filtrate in vacuo. Yield is 32 g. (100% theory). 

To an ice-cooled suspension of lead thiocyanate (485 mg, 1.5 mmol) in dry dichloromethane (10 ml) was added (dichloroiodo)benzene (330 mg, 1.2 mmol). The mixture was stirred for 20 min at 0°C and then the phenol (1 mmol) was added and the whole mixture was stirred for 1 h. The reaction mixture was filtered and silica (2 g) was added to the filtrate, which was concentrated. The product was adsorbed on silica and eluted with ethyl acetate-hexane to give the 4-thiocyanated phenol (61-95%) or naphthol (58-97%). In no case was any 2-isomer found. An alternative, more expensive, procedure for the thiocyanation of aromatics involved BTI (Section 4.5). 

Tetramethyl Tellurium6 A stirred suspension of 10.0 g (37 mmol) of powdered tellurium tetrachloride in 40 ml diethyl ether is cooled to — 78°. A solution of 155 mmol methyl lithium in diethyl ether(l 11 ml, 1.4 M) is dropped to the cool suspension. The reaction is warmed to 20° and stirred at this temperature in the dark for 12 h. The mixture is cooled to — 78° and filtered. The filter cake is washed with 25 ml diethyl ether. The filtrate and the washings are combined and fractionally distilled at 32° under a slight vacuum. The crude tetramethyl tellurium is collected at — 198° under vacuum and purified by vacuum distillation yield 77% b.p. 46 /20 torr. 

Sulphur dioxide may also be passed into a cooled suspension of zinc dust in water ... 

Bromo-2-chloro-3-hexylthiophene (0.0355 mol) was added over a period of 30 minutes to a mixture consisting of 75 ml of 2-methyltetrahydrofuran, magnesium (0.0355 mol), and 0.15 ml of IM t-butylmagnesium chloride solution in THF at 60°C to 70°C. The mixture was stirred for 90 minutes at 70°C. It was then cooled to 60°C and treated with a suspension of l,2-bis(diphenylphosphino)ethane nickel(II) chloride (0.177 mmol) in 12.5 ml of 2-methyltetrahydrofuran for over 30 minutes. The mixture was stirred an additional 3 hours at 80°C and further treated with triethylphosphite (3 mmol) and stirred for 30 minutes at 80°C. The mixture was then concentrated and the residue dissolved in 10 ml of toluene. This solution was poured into 100 ml of EtOAc, which created a suspension, and the suspension was stirred for 30 minutes at 80°C. The cooled suspension was filtered, the residue washed twice with 20 ml of EtOAc, and the product isolated in 81% yield having a Mn of 19,543 daltons with a of 224°C. 

O. 414 mole) and magnesium turnings (I I g., 0.458 g.-atom) is added 146 ml. (0.828 mole) of dry hexamethylphosphoramide (dried by distillation from calcium hydride). The resulting solution is blown over under a nitrogen atmosphere into the 500-ml. dropping funnel. The solution is slowly run into the cooled suspension where the methiodide salt dissolves. When the addition is complete, the reaction mixture is stirred at room temperature overnight. 

To a stirred, ice-cooled suspension of NaCl (1 g) in CISO3H (30 mL) was added in portions quinazolme-2,4-diamine sulfate (13.85 g, 0.05 mol). The resulting mixture was heated at 150-160 °C for 3 h, cooled, and then poured onto ice. The resulting precipitate was collected and washed with H O to afford 2,4-diamino-quinazoline-6-sulfonyl chloride as the sulfate salt yield 19.1 g (99%) mp >300°C,... 

Ethereal CHjNj [from A-mcthyl-A-nitrosotoluene-/)-sulfonamide (see Houben-Weyl. Vol. 10/4, pp 552-553), 21.5 g, 0.1 mol] was added to a stirred, ice-cooled suspension of 6-nitroquinoxalin-2(l//)-one (1.9 g, 9.9 mmol) in anhyd MeOH (20 mL). The mixture was stirred at 0 "C for 4 h, and then left overnight at 0 °C. The precipitate (0.95 g) was filtered off Crystallization (charcoal) from 96% EtOH and then from acetone gave l,3-dimethyl-6-nitro-l,2-dihydroquinoxalin-2(l/f )-one mp 219-222 C. The initial filtrate was evaporated in a vacuum. Crystallization of the residue from light petroleum (bp 60-80°C) and then benzene gave 2-methoxy-6-nitroquinoxaline mpl69-170°C. 

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