Cooling and evaporation

A solution of a benzene-1,2-diaminc (15mmol) and an cnol ether 4 (15mmol) in o-xylene (lOmL) was heated in a domestic microwave oven for a specified time. The reaction mixture was cooled and evaporated under reduced pressure, and the residue was purified by chromatography (silica gel. hexane/ CHCl3 1 4). 

A solution of a 4-cyclopropyl-l, 5-benzodiazepin-2-one4 (5.7 mmol) anti NCS orNBS (5.7 mmol) in CHC13 (50mL) was refluxed for 4h, cooled and evaporated under reduced pressure. The residue was chromatographed (silica gel) and recrystallized (Et20/benzene). 

Experimental Preparation of Spironaphthooxazine 33 (N-Bu). Tri-ethylamine (3.54 g, 35 mmol) was added to a suspension of 2,3,3-trimethyl-iV-butylindolinium iodide (12.0 g, 35 mmol) and o-nitrosonaphthol (6.1 g, 35 mmol) in EtOH (100 ml) under stirring. The mixture was refluxed for 2 h, cooled, and evaporated under reduced pressure. The residue was chromatographed on silica gel with benzene as an eluent, and then recrystallized from methanol to give spiro(Af-butylindolinonaphthooxazine) 33 (6.6 g, yield 51%). 

The feed to the crystallizer is saturated at 60°C (C = 2.867 kg sucrose-kg H20 1). Compare cooling and evaporative crystallization for the separation of sucrose from water. 

Gently reflux a suspension of 250 mg L-tryptophan in 10 g warm diphenylmethane in a stream of nitrogen (if possible) for 5-20minutes until there is no more C02 evolution. Cool and evaporate in vacuum or treat with 20 ml benzene saturated with dry HCI and filter, wash precipitate with hexane and dry to get about 60% yield of tryptamine. 

The combined filtrates containing benzonitrile oxide are transferred to a 1-1. round-bottomed flask, treated immediately with 13.9 g. (0.1 mole) of N-sulfinylaniline added in one portion, with swirling, and set aside protected from moisture, while the temperature reaches a maximum of 33-34° (usually IS minutes). The mixture is then heated to reflux, protected from moisture, in a temperature-controlled oil bath for 3-5 hours. Continuous evolution of sulfur dioxide takes place during this period at the end of which the mixture is cooled and evaporated under reduced pressure (Note 3) at 70-80° to remove the solvent. The residual dark brown liquid is transferred to a 50-ml., pear-shaped distilling flask (Note 13) and heated, protected from moisture, at 110° for 30 minutes to complete the decomposition. It is then cooled and distilled under high vacuum (Note 14). Unchanged N-sulfinylaniline (2.0-2.5 g.) distills over at 45-50° (0.1-0.2 mm.). A second fraction (1.2-1.5 g.) is collected until the temperature reaches 112° (Note 15) then diphenyl carbodiimide is collected at 114-117° (0.1-0.2 mm.) as a clear yellow liquid yield 10.5-10.8 g. (54-56%) (Note 16) 1.6355 ... 

Oxidation of tetrathioianes (8) with DMDO gave mixtures of dithiirane 1-oxides (10) and thioketones (11) (Scheme 5). The existence of the intermediate tetrathioiane 1-oxides (9) was verified by NMR of the cooled and evaporated reaction mixture. ... 

A mixture of 56.5 mmol of the 2/7-3,l-benzoxazine-2,4(l//)-dione 1 (R1 = H, CH3), 6.53 g (56.5 mmol) of pyridine hydrochloride and 7.15 g (62.2 mmol) of (S )-2-pyrrolidinecarboxylic acid is refluxed in pyridine for 6 h. After cooling and evaporation of the pyridine in vacuo, the resulting semisolid is partitioned between water and CHC13. The organic extract is washed with two 15-mL portions of 1M aq hydrochloric acid, followed by brine, and then dried over MgS04, filtered and concentrated to give a solid which, when triturated with ethyl acetate, gives the analytically pure product. 

A solution of 1.5g of rubidium carbonate is neutralized with pure 57% hydriodic acid ( No. 89), avoiding an excess of acid. The solution is warmed to 60°C and 2.5g of pure iodine is dissolved in it by stirring. The mixture is allowed to cool and evaporated in the air to dryness. 

A solution of 1 equivalent of isopropyl 5-p-methoxybenzoyl-l,2-dihydro-3H-pyrrolo[l,2-a]pyrrole-l-carboxylate in 10 ml of methanol is treated with a solution of 1 equivalent of potassium carbonate in 5 ml of water. The reaction mixture is refluxed under nitrogen atmosphere for 30 minutes, cooled, and evaporated to dryness. The residue is taken up in 10 ml of 10% aqueous hydrochloric acid and 50 ml of water and the resultant mixture extracted with ethyl acetate (2x50 ml). The combined extracts are dried over magnesium sulfate and evaporated to dryness under reduced pressure. Crystallization of the residue from ethyl acetate-hexane affords 5-p-methoxybenzoyl-l,2-dihydro-3H-pyrrolo[l, 2-a]pyrrole-l-carboxylic acid (anirolac) MP 187°-187.5°C. 

A mixture of 10.3 parts of l-chloro-4-(chloromethyl)-2-nitrobenzene, 25.2 parts of l-(diphenylmethyl)piperazine and 120 parts of ethanol is stirred and refluxed for 4 h. The reaction mixture is cooled and evaporated. The residue is taken up in about 100 parts of water and the product is extracted with methylbenzene. The extract is washed with water, dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using trichloromethane as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from a mixture of 2,2 -oxybispropane and hexane (1 2 by volume). The product is filtered off, washed with hexane and dried, yielding 19.6 parts of l-(4-chloro-3-nitrophenylmethyl)-4-(diphenylmethyl)piperazine melting point 101.6°C. 

To a solution of 101.2 g of the trimethoxy secondary amine, obtained as described above, in 3,060 ml of glacial acetic acid was added 1,225 ml of 48% hydrobromic acid and the reaction mixture heated at the reflux temperature for 4 hours. The reaction mixture was then cooled and evaporated to a small volume. The crystalline residue which formed was filtered and dried in vacuo. The dried crystalline residue was then triturated with ethyl acetate and redried to yield 97.3 g of crude crystalline material. 

A solution of 2.0 g of 4-(4-chloro-4-p-cyanophenyl-n-butyl)-lH-imidazole in 50 ml of chloroform is refluxed for 4 hours under nitrogen, cooled and evaporated to yield the 5-p-cyanophenyl-5,6,7,8-tetrahydroimidazo[l,5-a]... 

A solution of 4.5 g of 4-(4-p-t-butylaminocarbonylphenyl-4-hydroxy-n-butyl)-1-trimethylsilylimidazole in 50 ml of thionyl chloride is refluxed for 1 hour, cooled and evaporated. The residue is partitioned between methylene chloride and aqueous sodium bicarbonate solution. The organic phase is separated, dried over sodium sulfate and evaporated to yield the title compound (c). 

A solution of l-(phenylmethyleneamino)isatin (1.354 g, 0.0054 mol) and endo-3-amino-9-methyl-9-azabicyclo[3.3.1]nonane (0.832 g, 0.0054 mol) in dry THF (25 ml) under argon was heated to reflux for 5 hours. The solution was cooled and evaporated and the residual traces of THF were azeotropically removed with dichloromethane. The residue was triturated with ether to give the intermediate 2-(benzylidenehydrazino)-a-oxophenyl-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)carboxamide as an orange powder (1.583 g, 73%). 

A mixture of norcodeine hydrochloride (11.48 g, 27.8 mmol), (chloromethyl)cyclopropane (5.14 g, 55.6 mmol), sodium carbonate (14.73 g, 139.0 mmol), and potassium iodide (4.61 g, 27.8 mmol) in ethanol (250 ml) was heated at reflux for 20 hr, cooled, and evaporated in vacuo to dryness. The residue was basified with NH4OH, and extracted with methylene chloride. The extract was washed with water and evaporated in vacuo to dryness. The residue (11.7 g) was chromatographed on silica gel with a eluting solvent system of methanol/ethyl acetate (10/90) to give 17-cyclopropylmethylnorcodeine (10.68 g, 91% yield). 

A suspension of 300 mg of adriamycin-14-valerate hydrochloride in 20 ml of ethyl acetate was treated with 0.45 ml of trifluoroacetic anhydride in small portions over a few minutes until all solids had dissolved. The solution was mixed immediately with equal portions of water and chloroform (total volume 100 ml). The chloroform layer was separated and washed once with water and twice with pH 7 aqueous buffer. The chloroform solution was dried over sodium sulfate and then was evaporated to dryness under reduced pressure. The residue was dissolved in 25 ml of methanol, and the resulting solution was heated at reflux for 5 minutes, then cooled and evaporated to dryness. The residue was redissolved in 4 ml of chloroform, and the crude product was precipitated by the addition of 20 ml of petroleum ether (b.p. 38°-49°C). The crude material was purified by chromatography on a silicic acid column. 

Difiuorodiiodomethane (30.4 g, 100 mmol) was carefully added dropwise to a solution of (EtO)jP (1 16.6 g, 100 mmol) in anhyd Et20 (25 mL) at 0 C. After complete addition, the mixture was refluxed for 5 h. After cooling and evaporation of solvent, the oily residue was subjected to column chromatography (silica gel, petroleum cthcr/EtOAc 3 1) to furnish pure 2 yield 30.1 g (96%). 

In 6-XXII (MNP) the four different forms may be obtained from different solvents under different rates of cooling and evaporation. The space groups for the two forms for which crystal structures have been reported (Forms 2 and 3) are again both non-centrosymmetric monoclinic P2. The needles of Form 2 obtained by rapid cooling... 

A mixture of 1,2,3-tri-tert-butylcyclopropenylium tetrafluoroborate (0.50 g, 1.7 mmol) and bis(triphenyl-phosphoranylidene)ammonium tricarbonylnitrosylferrate (1.20 g, 1.7 mmol) in THE (50 mL) was refluxed for 5 h, then cooled, and evaporated to dryness. The residue was extracted with hexane until no further orange solution was obtained, and the extraets were filtered through a short Florisil plug. The filtrate was evaporated and the residue recrystallized (hexanes at — 60°C) which gave orange crystals yield 0.563 g (95%) mp 155 C (dec.). 

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