Residual methoxy

Polymer-melamine crosslinks are also broken during exposure to UV light. Although some crosslink scission occurs in the dark by direct hydrolysis, the rate of scission (as measured by the rate of disappearance of residual methoxy functionality) Increases dramatically with Increasing UV light Intensity (11). Scission occurs with UV light in the absence of humidity but at a much reduced rate. 

LD-FTICR-MS spectrum of StyrEomer-2100, a poly(ethylene oxide) methyl ether styrene oligomer. The solid line represents the distribution from residual methoxy-capped poly(ethylene oxide). (Reproduced from ref. 57 with permission of the copyright holder)... 

A solution of 0.22 mol of butyllithium in 150 ml of hexane was cooled below -40°C and 140 ml of dry THF were added. Subsequently 0.20 mol of 1-dimethyl amino--4-methoxy-2-butyne (see Chapter V, Exp. 14) were added in 10 min with cooling between -35 and -45°C. After an additional 15 min 100 ml of an aqueous solution of 25 g of ammonium chloride were added with vigorous stirring. After separation of the layers four extractions with diethyl ether were carried out. The solutions were dried over potassium carbonate and then concentrated in a water-pump vacuum. Distillation of the residue gave a mixture of 8-10% of starting compound and 90-92% of the allenic ether, b.p. 50°C/12 mmHg, n 1.4648, in 82% yield (note 1). 

A solution of At-(tcrt-butoxycarbonyl)-6-methoxy-2-methylaniline (11.9 g, 50 mmol) was cooled to — 40°C and s-BuLi (96 ml of 1.3 M in cyclohexane. 125mmol) was added. The mixture was stirred at —45°C to —55°Cfor 30min and then allowed to warm slowly to — 15"C over 60 min. The yellow solution was recooled to —45 C and DMF (5.8 ml, 75 mmol) was added. After 5 min the reaction mixture was diluted with water (250 ml) and the product was extracted with EtOAc (2 x 150 ml). The extract was washed with w ater (200ml) and then concentrated in vacuo. The residue was dissolved in THF (100 ml) and 12 N HCl (2 ml) was added. The solution was stirred for 5 min at room temperature and then diluted with ether (250 ml). The solution was washed with water (250 ml), sat. aq. NaHCOj (250 ml), and brine (250 ml), dried (Na2S04) and evaporated. The product was purified by chromatography using 2% EtOAc in hexane for elution. The yield (9.3 g) was 75%. 

A solution of 2,3-dibromo-5-methoxyaniline (32 g, 0.17 mol) in CHjClj (300 ml) was stirred and cooled in an icc bath. Boron trichloride (1 M in CH2CI2, 180 ml, 0.18 mol), chloroacetonitrile (14.3 g, 0.19 mol) and TiC (1 M in CH CIj, 190ml, 0.19 mol) were added. The resulting mixture was refluxed for 1.5 h. The solution was cooled to room temperature and poured carefully on to a mixture of icc and 20% aq. HCl (700 ml). The organic layer was separated and the CH Clj removed by distillation. The residue was heated to 90°C on a water bath for 30 min. The solution was cooled and the solid collected by filtration. It was partitioned between ether (1.41) and 1 N NaOH (500 ml). The ether layer was washed with brine, dried over Na2S04 and evaporated. The residue was recrystallized from ethanol to give 2-amino-3,4-dibromo-6-methoxy-a-chloroacetophenone (55 g) in 90% yield. 

Methoxyurldlne-2,3,S-trl-0 benzoate (4).3 To 5-methoxy-2,4-bis(tnmethylsiiyloxy)uracil 1(11 mmol, 34 mL of 0 356 N solution In 1,2-dichioroethane) and 1-0-acetyl-2,3,5-lrl-0-benzoyl-p 0-ribofuranose 2 (5 04 g, 10 mmol) in dichioroethane (75 mL) was added trimethyisllyl inflate 3(12 mmol, 22 8 mL of 0 522 N solution in dichioroethane) and the mixture was stirred lor 4 h at 2S C The clear yellow solution was diluted with CH2CI2 (50 mL) extracted with an ice cooled solution of NaHCOa (50 mL) and after washing with water (2x20 mL), the organic phase was dned (Na2S04), the solvent evaporated and the residue recrystallized from EtOAc-hexane to afford 5 24 g of 4 (89%), mp 205-207°C... 

Ji-Methoxy-ll, 11-ethylenedioxy-lS-methylestra-1,3,5(lO)-tnene. A solution of (+)3-methoxy-18-methylestra-l,3,5(10)-trien-17-one (5 g) dissolved in ethylene glycol (5 ml) and ethyl orthoformate (10 ml) containing />-toluenesulfonic acid (0.3 g) is heated under reflux for 2 hr in a nitrogen atmosphere. The resulting solution is diluted with methylene chloride and washed with dilute sodium bicarbonate and water. The organic phase is dried over sodium sulfate and evaporated to dryness in the presence of a trace of pyridine. Trituration of the residue with petroleum ether yields 4.7 g (82 %) of the pure ketal. 

Methoxy-cis-19-norpregna-l,3,5(10),17(20)-tetraene A solution of 31 g (109 mmolesi of estrone methyl ether in 600 ml of benzene is added rapidly to a solution of 469 mmoles of ethylidenetriphenylphosphorane in 1.2 liters of DMSO. After heating under nitrogen at 60° overnight, the reaction is cooled, poured into ice water, and extracted with three portions of hexane, backwashed with three portions of water and the hexane removed. The crude product, dissolved in petroleum ether (bp, 30-60°), is filtered through 225 g of alumina (activity I). The residue from the eluate consists of 95 % cis- and 5 % tran5-isomers, as determined by vpc analysis. After recrystallization from ether-methanol, 26.3 g (82%) of cw-isomer is obtained mp 76.5-77.5° [a]o 60°. 

Bromo-4-methoxy-A-homo-estra-2,4,5(10)-trien-17-one (44 0. 2g), is dissolved in formic acid, 2 ml of boron trifluoride etherate is added and the mixture is stirred vigorously at 0° for 2 hr. A brown mass ca. 0.12 g) is obtained after evaporation of the solvents at reduced pressure. This material is diluted with water and extracted with chloroform. The chloroform extracts are washed successively with water and saturated salt solution, dried over anhydrous magnesium sulfate and evaporated at reduced pressure to give 95 mg of a product which is purified by filtration through a column of neutral alumina and crystallization of the residue after evaporation of the solvent from ethyl acetate-petroleum ether. The resulting A-homo-estra-l(10),2,4a-triene-4,17-dione (45), mp 143-146°, is identical to the tropone (45) prepared from monoadduct 17-ketone (43a). 

A solution of the crude cyanohydrin (94a ca. 1 g) in pyridine (15 ml) and acetic anhydride (15 ml) is allowed to stand at room temperature for 52 hr. The solvents are evaporated under reduced pressure below 60°. The residue is dissolved in ether, and the ether solution is washed successively with 5 % hydrochloric acid, water and saturated salt solution. The solvent is evaporated under reduced pressure to give a crystalline residue. Recrystallization of the crude product from cyclohexane-acetone gives 3-methoxy-17a-cyano-estra-l,3,5(10)-trien-17i5-ol acetate (94b 0.9 g), mp 130-132°, as large prisms. 

To a solution of vanillin in toluene is added nitroethane, butylamine and glacial acetic acid. The mixture is refluxed and the water of reaction is steadily azeotropically removed by distillation. After the theoretical amount of water is distilled out, distillation Is continued to remove excess reactants. The last trace of excess reactants is then removed at room temperature under a vacuum. The product is then triturated with a hydrocarbon solvent such as Skellysolve B and is thus obtained in a crystalline state. In general, however, it is preferred to dissolve the residue directly In toluene for use in the next step, without isolating the 1-(2-nitropropen-1-y I )-4-hydroxy-3-methoxy benzene. 

Benzhydryl 3-carbamoyloxymethyl-7j3-(2-thienylacetamido)-70 -methoxydecephalosporanate (300 mg) in 0.5 ml in anisole and 2.5 ml of trifluoroacetic acid is reacted for 15 minutes at 10°C. The resulting mixture is evaporated at reduced pressure and flushed twice with anisole. The residue is dissolved in methylene chloride and extracted with 5% sodium bicarbonate solution. The aqueous solution is adjusted to pH 1. B with 5% phosphoric acid and extracted with ethyl acetate. The organic solution is dried and evaporated to yield the pure 3-carba-moyloxymethyl-70 -methoxy-7/3-(2-thienylacetamido)decephalosporanic acid, MP 165°C to 167°C. This may then be converted to the sodium salt. 

Orthoesterification A mixture of 1 g of 6a a-difiuoroprednisolone, 10 mg of p-toluene-suifonic acid, 5 cc of dimethylformamide and 3 cc of methyl orthobutyrate is heated for 15 hours on an oil bath at 105°C while a slow stream of nitrogen is passed through the mixture so that the methanoi produced as a by-product of the reaction, is distilled off. After addition of severai drops of pyridine to neutralize the acid catalyst, the reaction mixture is evaporated under vacuum and there is obtained a solid residue which is taken up with methanol, and filtered. The product is recrystailized from a methylene chloride-methanol mixture to yieid 682 mg of 6a,9af[Pg.491]

A solution of 50 grams of N-(a-methylhomoveratryl)-3-methoxy-4-ethoxyphenylacetamide, prepared as set out above, in 200 cc of benzene, is treated with 8 cc of phosphorus oxychloride. The mixture is refluxed for about 3 hours, cooled and then is shaken with a solution composed of 15 grams of sodium hydroxide dissolved in 60 cc of water. The aqueous layer is removed, and the benzene solution is washed with water. The washed benzene solution is dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The low-melting solid residue is 6,7-dimethoxy-3-methyl-1-(3 -methoxy-4 -ethoxybenzyl)-dihydroisoquinoline base. 

A mixture of 16.3 g of 4-methyl-6-methoxy-2-pyrimidinyl-hydrazine, 13.7 g of ethyl acetoacetate and 16.3 ml of methanol was refluxed 2 hours on a water bath. After a mixture of 4.7 g of sodium hydroxide, 4.7 ml of water and 27 ml of methanol was added dropwise thereto at about 50°C, the reaction mixture was refluxed for 2 hours more, then methanol was distilled off and the residue was dissolved in 130 ml of water. The solution was adjusted to pH 6 with acetic acid. The precipitate was filtered, washed with water and dried to give 24 g (yield 95.3%) of crystals, MP 97° to 98°C. Recrystallization from ligroin gave 1-(4 -methyl-6 -methoxy-2 -pyrimidinyl)-3-methyl-3-pyrazoline-5-one, MP 102° to 103°C. 

To a solution of 4.76 g of 1-(4 -methyl-6 -methoxy-2 -pyrimidinyl)-3-methyl-3-pyrazoline-5-one in 200 ml of ether was added an ether solution containing 6 molar equivalents of diazomethane and the reaction mixture was allowed to stand at room temperature for 20 hours. After distilling off the solvent, the residue was dissolved in 160 ml of water, made alkaline (pH 10) with sodium hydroxide solution and extracted three times with 140 ml of benzene. The extract was washed with a small amount of water, dried over sodium sulfate and evaporated to give a crystalline mass. Recrystallization from isopropylether gave 1-(4 -methyl-6 -methoxy-2 -pyrimidinyl)-3-methyl-5-methoxypyrazole (3.96 g, 84%) as colorless prisms, MP 90° to 92°C. 

Stage 2 Preparation of 1 -[2-Phenyi-2-Methoxy]-Ethyi-Piperazine — 210 grams of 2-phenyl-2-methoxy-ethyl bromide and 260 grams of anhydrous piperazine are heated for 5 to 6 hours to reflux in 600 ml of ethanol, 500 ml of ethanol is then distilled off and finally the solvent is removed in vacuo. The residue is taken up in 250 ml of benzene and the piperazine hydrobromide is filtered off. The benzene is removed in vacuo. The oily residue is taken up by 450 ml of water and acidification is effected up to pH = 1 by concentrated HCI. 

A) 2-Methyl-5-Methoxy-3-lndolylacetic Anhydride Dicyclohexylcarbodiimide (10 g, 0.049 mol) is dissolved in a solution of 2-methyl-5-methoxy-3-indolylacetic acid (22 g, 0.10 mol) in 200 ml of THF, and the solution Is allowed to stand at room temperature for 2 hours. The precipitated urea is removed by filtration, and the filtrate is evaporated in vacuo to a residue and flushed with Skellysolve B. The residual oily anhydride is used without purification in the next step. 

B) t-Butyl 2-Methyl-5-Methoxy-3-lndolylacetate t-Butyl alcohol (25 ml) and fused zinc chloride (0.3 g) are added to the anhydride from Part A. The solution is refluxed for 16 hours and excess alcohol is removed in vacuo. The residue is dissolved in ether, washed several times with saturated bicarbonate, water, and saturated salt solution. After drying over magnesium sulfate, the solution is treated with charcoal, evaporated, and flushed several times with Skellysolve B for complete removal of alcohol. The residual oily ester (18 g, 93%) is used without purification. 

The chloroform solution is concentrated and the residue recry stall i2ed from 270 cc of absolute ethanol. The pure 10-methoxy-4-(1 -methyl-4-piperldyl)-4H-ben2o[4,5] cyclohepta[1,2-b] -thiophen-4-ol base, having a melting point of 194°C to 196°C, is obtained in this manner. Microanalysis corresponds with the formula Q20H23NO2S. 

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