1,4-dichlorobutane

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 8.6 g of magnesium chips was placed in 75 ml of tetrahydrofuran. Then a mixture of 3.2 of 1,2-dibromoethane and 2.5 g of 1,4-dichlorobutane in 35 ml of tetrahydrofuran was added within 15 minutes so that the temperature could be kept between 30° and 35° C. Then another 20.5 g of 1,4-dichlorobutane in 75 ml of tetrahydrofuran was added within 30 minutes. The reaction mixture was stirred for 3 hours at this temperature and then mixed with 9 g of tetramethylethylenediamine and 180 ml of tetrahydrofuran. The reaction solution was cooled to -40° to -45° C. and then mixed with a solution of 30 g of (3aS,6aR)-1-[(R)-(1-phenylethyl)]-3-benzyl-dihydro-1H-thieno-[ 3,4-d]-imidazol-2,4(3H,3aH)-dione in 180 ml of tetrahydrofuran within 20 minutes. It was stirred at this temperature for 1 hour and then CO2 gas was introduced for 30 minutes. The reaction mixture was poured onto 400 ml of 10 percent aqueous sulfuric acid and extracted several times with toluene. The toluene phase was mixed with 0.8 g of conc. Sulfuric acid, washed with water and concentrated on a rotary evaporator. The residue was mixed with 400 ml of 10 percent potassium carbonate solution and extracted with ethyl acetate. The organic phase was washed again with 10 percent potassium carbonate solution. The combined aqueous phases were adjusted to pH 7.3 with aqueous sulfuric acid and extracted several times with ethyl acetate. The organic phase was finally dried with magnesium sulfate and concentrated. The product was precipitated by addition of hexane, filtered off and dried. 32.5 g (89.3 percent) of the title product was obtained as snow-white powder with a content (HPLC) of more than 99 percent. Concerning the product: Melting point: 101.0°-102.0° C. was added within 15 minutes so that the temperature could be kept between 30° and 35° C The reaction solution was cooled to -40° to -45° C. It was stirred at this temperature for 1 hour extracted several times with toluene The toluene phase was mixed with 0.8 g of conc. Sulfuric acid washed with water concentrated on a rotary evaporator The residue was mixed with 400 ml of 10 percent potassium carbonate solution extracted with ethyl acetate The organic phase was washed again with 10 percent potassium carbonate solution extracted several times with ethyl acetate The organic phase was finally dried with magnesium sulfate concentrated The product was precipitated by addition of hexane filtered off dried

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred mixture of 13.2 parts of 2-methyl-1H-benzimidazole, 3 parts of N,N,N-triethylbenzenemethanaminium chloride and 225 parts of a sodium hydroxide solution 60% are added 25 parts of 1,4-dichlorobutane. The whole is heated to about 100° C. and stirring is continued for one hour at this temperature. The reaction mixture is cooled and poured onto ice-water. The product is extracted with methylbenzene. The extract is dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (90:10) as eluent. The pure fractions are collected and eluent is evaporated, yielding 1-(4-chlorobutyl)-2-methyl-1H-benzimidazole as a residue. The reaction mixture is cooled poured onto ice-water The product is extracted with methylbenzene The extract is dried filtered evaporated The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (90:10) as eluent The pure fractions are collected eluent is evaporated

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Mixture of 6-hydroxyindan-1-one of the formula (11) (20 gm, 0.135 mol), potassium carbonate (40 gm, 0.289 mol), 1,4-dichlorobutane (80 ml, 0.73 mol) and tetrabutyl ammonium bromide (2 g) was stirred for 1-3 hrs at 95° C. then distilled off excess 1,4-dichloro butane, diluted with water (80 ml). The aqueous layer was extracted with ethyl acetate, and the extract was washed with water, dried and evaporated off under reduced pressure to dryness. The evaporation residue is purified by crystallization using isopropyl ether as a solvent gave 29.5 gm of novel 6-(4-CHLORO BUTOXY)-INDAN-1-ONE of the formula (3). then distilled off excess 1,4-dichloro butane diluted with water (80 ml) The aqueous layer was extracted with ethyl acetate the extract was washed with water dried evaporated off under reduced pressure to dryness The evaporation residue is purified by crystallization

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Mixture of 6-hydroxyindan-1-one of the formula (11) (20 gm, 0.135 mol), potassium carbonate (40 gm, 0.289 mol), 1,4-dichlorobutane (80 ml, 0.73 mol) and tetrabutyl ammonium bromide (2 g) was stirred for 1-3 hrs at 95° C. then distilled off excess 1,4-dichloro butane, diluted with water (80 ml). The aqueous layer was extracted with ethyl acetate, and the extract was washed with water, dried and evaporated off under reduced pressure to dryness. The evaporation residue is purified by crystallization using isopropyl ether as a solvent gave 29.5 gm of novel 6-(4-CHLORO BUTOXY)-INDAN-1-ONE of the formula (3). then distilled off excess 1,4-dichloro butane diluted with water (80 ml) The aqueous layer was extracted with ethyl acetate the extract was washed with water dried evaporated off under reduced pressure to dryness The evaporation residue is purified by crystallization

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 8.6 g of magnesium chips was placed in 75 ml of tetrahydrofuran. Then a mixture of 3.2 g of 1,2-dibromoethane and 2.5 g of 1,4-dichlorobutane in 35 ml of tetrahydrofuran was added within 15 minutes so that the temperature could be kept between 30° and 35° C. Then another b 20.5 g of 1,4-dichlorobutane in 75 ml of tetrahydrofuran was added within 30 minutes. The reaction mixture was stirred for 3 hours at this temperature and then mixed with 9 g of tetramethylethylenediamine and 180 ml of tetrahydrofuran. The reaction solution was cooled to -40° to -45° C. and then mixed with a solution of 30 g of (3aS,6aR)-1-[(R)-(1-phenylethyl)]-3-benzyl-dihydro-1H-thieno[3,4-d]imidazol-2,4(3H,3aH)-dione in 180 ml of tetrahydrofuran within 20 minutes. It was stirred at this temperature for 1 hour and then CO2 gas was introduced for 30 minutes. The reaction mixture was poured onto 400 ml of 10 percent aqueous sulfuric acid and extracted several times with toluene. The toluene phase was mixed with 0.8 g of conc. sulfuric acid, washed with water and concentrated on a rotary evaporator. The residue was mixed with 400 ml of 10 percent potassium carbonate solution and extracted with ethyl acetate. The organic phase was washed again with 10 percent potassium carbonate solution. The combined aqueous phases were adjusted to pH 7.3 with aqueous sulfuric acid and extracted several times with ethyl acetate. The organic phase was finally dried with magnesium sulfate and concentrated. The product was precipitated by addition of hexane, filtered off and dried. 32.5 g (89.3 percent) of the title product was obtained as snow-white powder with a content (HPLC) of more than 99 percent. Concerning the product: Melting point: 101.0°-102.0° C. was added within 15 minutes so that the temperature could be kept between 30° and 35° C The reaction solution was cooled to -40° to -45° C. It was stirred at this temperature for 1 hour extracted several times with toluene The toluene phase was mixed with 0.8 g of conc. sulfuric acid washed with water concentrated on a rotary evaporator The residue was mixed with 400 ml of 10 percent potassium carbonate solution extracted with ethyl acetate The organic phase was washed again with 10 percent potassium carbonate solution extracted several times with ethyl acetate The organic phase was finally dried with magnesium sulfate concentrated The product was precipitated by addition of hexane filtered off dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A two phase mixture of phenol (5 g, 53 mmol), 1,4-dichlorobutane (30 ml), tetrabutylammonium hydrogen sulphate (0.3 g, 1 mmol), and sodium hydroxide solution (25 ml, 6M) was refluxed for 3 h. The organic layer was separated, dried (MgSO4), and concentrated in vacuo. The residues were purified by flash chromatography (silica (Merck 15111); eluant:petrol) to give the product as a colourless viscous oil (7.57 g 77%) bp 250° C. at 0.2 mm Hg. was refluxed for 3 h The organic layer was separated dried (MgSO4) concentrated in vacuo The residues were purified by flash chromatography (silica (Merck 15111); eluant:petrol)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A two phase mixture of phenol (5 g, 53 mmol), 1,4-dichlorobutane (30 ml), tetrabutylammonium hydrogen sulphate (0.3 g, 1 mmol), and sodium hydroxide solution (25 ml, 6M) was refluxed for 3 h. The organic layer was separated, dried (MgSO4), and concentrated in vacuo. The residues were purified by flash chromatography (silica (Merck 15111); eluant:petrol) to give the product as a colourless viscous oil (7.57 g 77%) bp 250° C. at 0.2 mm Hg. was refluxed for 3 h The organic layer was separated dried (MgSO4) concentrated in vacuo The residues were purified by flash chromatography (silica (Merck 15111); eluant:petrol)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture comprising 500 mg of N-tert-butoxycarbonyl-trans-1,4-cyclohexanediamine, 326 mg of 1,4-dichlorobutane, 805 mg of potassium carbonate, 70 mg of sodium iodide and ethanol-water (8 ml–2 ml) was stirred at 90° C. for 12 days. Water was added to the reaction mixture, and the resulting mixture was extracted with chloroform. The extract was washed with brine, dried over anhydrous sodium sulfate, and then, the solvent was removed under reduced pressure. The obtained residue was purified by silica gel flash column chromatography (solvent: chloroform-methanol-aqueous ammonia=100/5/0.5 to 100/10/0.5) to obtain 453 mg of N-tert-butoxycarbonyl trans-4-(1-pyrrolidinyl)cyclohexylamine. the resulting mixture was extracted with chloroform The extract was washed with brine dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The obtained residue was purified by silica gel flash column chromatography (solvent: chloroform-methanol-aqueous ammonia=100/5/0.5 to 100/10/0.5)