4-ethylcyclohexan-1-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 12.6 g of 4-ethylcyclohexanone, 17.0 g of diethyl aminomethylenemalonate, and 950 mg of p-toluenesulfonic acid in 170 ml of toluene is heated at reflux for 48 hours with a water separator, under nitrogen atmosphere. The solvent is removed under nitrogen atmosphere and under vacuum, and the residue purified by flash column chromatooraphy on a silica qel column eluted with methylene chloride. The desired product, diethyl N-(4-ethylcyclohexen-1-yl)-aminomethylenemalonate is obtained as an oil. The purified product in 90 ml Dowtherm is aded to 300 ml Dowtherm preheated to 250° under nitrogen atmosphere. After heating at 240°-245° for 4 hours the reaction mixture is cooled and allowed to stand at room temperature overnight. The precipitate which formed is filtered off, washed with hexane and air-dried. Recrystallization form isopropanol after treatment with decolorizing carbon affords ethyl 4-hydroxy-6-ethyl-5,6,7,8-tetrahydroquinoline-3-carboxylate m.p. 218°-220°. is heated The solvent is removed under nitrogen atmosphere and under vacuum the residue purified by flash column chromatooraphy on a silica qel column eluted with methylene chloride

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In 50 ml of anhydrous ethanol were dissolved 35.4 g of p-diethylaminobenzaldehyde and 12.6 g of 4-ethylcyclohexanone, and 20 ml of 10% ethanolic solution of sodium ethoxide was added dropwise to the resulting solution, and the resulting mixture was subjected to reaction under reflux for 12 hours. The reaction mixture was cooled, and the crystals thus precipitated were collected by filtration and then recrystallized from toluene, to obtain 15.8 g of 2,6-bis(4'-diethylaminobenzal)-4-ethylcyclohexanone (m.p. 141° C.). was added dropwise to the resulting solution the resulting mixture was subjected to reaction under reflux for 12 hours The reaction mixture was cooled the crystals thus precipitated were collected by filtration recrystallized from toluene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In 50 ml of anhydrous ethanol were dissolved 35.4 g of p-diethylaminobenzaldehyde and 12.6 g of 4-ethylcyclohexanone, and 20 ml of 10% ethanolic solution of sodium ethoxide was added dropwise to the resulting solution, and the resulting mixture was subjected to reaction under reflux for 12 hours. The reaction mixture was cooled, and the crystals thus precipitated were collected by filtration and then recrystallized from toluene, to obtain 15.8 g of 2,6-bis(4'-diethylaminobenzal)-4-ethylcyclohexanone (m.p. 141° C.). was added dropwise to the resulting solution the resulting mixture was subjected to reaction under reflux for 12 hours The reaction mixture was cooled the crystals thus precipitated were collected by filtration recrystallized from toluene

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 91.6 g of 4-Ethyl-cyclohexanone, 73.6 g of morpholine and 2 g of p-toluene-sulfonic acid monohydrate are dissolved in 400 ml of toluene. The mixture is heated to reflux and the water formed is removed by a water separator. After reacting for about 24 h, the reaction mixture is cooled to 100° C. and 2 g of p-toluene-sulfonic acid are added, followed by the addition of 157.22 g of glyoxylic acid ethyl ester during 30 minutes. The mixture is again heated to reflux for 5 hours and allowed to cool down to 22° C. The solvent is evaporated in vacuo and the crude product is distilled in vacuo at 140-150° C./9.5−2 mbar. The mixture is heated to reflux is removed by a water separator 2 g of p-toluene-sulfonic acid are added followed by the addition of 157.22 g of glyoxylic acid ethyl ester during 30 minutes The mixture is again heated to reflux for 5 hours to cool down to 22° C The solvent is evaporated in vacuo the crude product is distilled in vacuo at 140-150° C./9.5−2 mbar

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared as a white solid from reaction of (N-Azetidin-3-yl-2-(5-trifluoromethyl-benzo[d]isoxazol-3-ylamino)-acetamide TFA salt (as prepared in Example 1, Step D) and 4-ethyl-cyclohexanone using the procedure described in Step E of Example 1.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 12.6 g of 4-ethylcyclohexanone, 17.0 g of diethyl aminomethylenemalonate, and 950 mg of p-toluenesulfonic acid in 170 ml of toluene is heated at reflux for 48 hours with a water separator, under nitrogen atmosphere. The solvent is removed under nitrogen atmosphere and under vacuum, and the residue purified by flash column chromatography on a silica gel column eluted with methylene chloride. The desired product, diethyl N-(4-ethylcyclohexen-1-yl)-aminomethylenemalonate is obtained as an oil. The purified product in 90 ml Dowtherm is aded to 300 ml Dowtherm preheated to 250° under nitrogen atmosphere. After heating at 240°-245° for 4 hours the reaction mixture is cooled and allowed to stand at room temperature overnight. The precipitate which formed is filtered off, washed with hexane and air-dried. Recrystallization form isopropanol after treatment with decolorizing carbon affords ethyl 4-hydroxy-6-ethyl-5,6,7,8-tetrahydroquinoline-3-carboxylate m.p. 218°-220°. is heated The solvent is removed under nitrogen atmosphere and under vacuum the residue purified by flash column chromatography on a silica gel column eluted with methylene chloride

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Malonic acid (5.2 g, 0.05 mol) and concentrated sulfuric acid (0.5 ml) were added to acetic anhydride (10 ml), and therein the source compound was dissolved thoroughly while stirring at room temperature. Thereto, 4-ethylcyclohexanone (6.31 g, 0.05 mol) was slowly added dropwise while cooling in an ice bath. The stirring of the admixture was continued in an ice bath, and colorless crystals separated out as the reaction progressed. These crystals were filtered off, washed with distilled water, and dried. Thus, 9.0 g of a meldrum's acid derivative was obtained as colorless crystals (in a 85.1% yield). The thus obtained meldrum's acid derivative (4.25 g, 0.02 mol) and N,N′-1,3-pentadiene-1-yl-5-ylidenedianiline hydrochloride (5.70 g, 0.02 mol) were dissolved in methanol (50 ml), and thereto triethylamine (3.04 g, 0.03 mol) was added. The stirring of the resulting admixture was continued at room temperature to result in deposition of violet crystals. Then, these crystals were filtered off, and washed with methanol. Thus, 5.61 g of violet crystals corresponding to Compound (3-I) was obtained (in a 76.3% yield). These violet crystals (4.40 g, 12.0 mmol) and the Compound (1-I) obtained in the foregoing Synthesis (1.71 g, 6.0 mmol) were dissolved in dimethylformamide (20 ml), and thereto triethylamine (1.82 g, 18 mmol) was added dropwise. The resulting admixture was stirred for 4 hours at 50° C. Thereafter, the reaction solution obtained was admixed with distilled water, and extracted with ethyl acetate. The organic layer thus extracted was purified by column chromatography (dichloromethane/methanol=6/1) on silica gel to give 2.0 g of violet powder corresponding to Compound (3-II) (in a 39.5% yield). the source compound was dissolved thoroughly while cooling in an ice bath The stirring of the admixture was continued in an ice bath colorless crystals separated out as the reaction These crystals were filtered off washed with distilled water dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 12.6 g of 4-ethylcyclohexanone, 17.0 g of diethyl aminomethylenemalonate, and 950 mg of p-toluenesulfonic acid in 170 ml of toluene is heated at reflux for 48 hours with a water separator, under nitrogen atmosphere. The solvent is removed under nitrogen atmosphere and under vacuum, and the residue purified by flash column chromatography on a silica gel column eluted with methylene chloride. The desired product, diethyl N-(4-ethylcyclohexen-1-yl)-aminomethylenemalonate is obtained as an oil. The purified product in 90 ml Dowtherm is added to 300 ml Dowtherm preheated to 250° under nitrogen atmosphere. After heatinq at 240°-245° for 4 hours the reaction mixture is cooled and allowed to stand at room temperature overnight. The precipitate which formed is filtered off, washed with hexane and air-dried. Recrystallization form isopropanol after treatment with decolorizing carbon affords ethyl 4-hydroxy-6-ethyl-5,6,7,8-tetrahydroquinoline-3-carboxylate m.p. 218°-220°. is heated The solvent is removed under nitrogen atmosphere and under vacuum the residue purified by flash column chromatography on a silica gel column eluted with methylene chloride