4-(diethylamino)butanoic acid;hydrochloride

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

実験手順: A solution of 3-dimethylamino-1,1-diphenyl-propan-2-ol (2 55g) 4-diethylaminobutyric acid hydrochloride (1 95g.) and dicyclohexylcarbodiimide (2.1g.) in dichloromethane (50 ml) was stirred at room temperature for 5 days Dicyclohexylurea was filtered off and the filtrate concentrated. The residue was dissolved in dilute hydrochloric acid and ether. The acid extract was basified; isolation through ether in the normal manner gave an oil which was chromatographed as alumina (200g.). Elution with progressively graded mixtures of light petroleum and ether gave the 4-diethylaminobutyrate of 3-dimethylamino-1,1-diphenyl-propan-2-ol isolated as the dihydrochloride (41%) as a glass was filtered off the filtrate concentrated The residue was dissolved in dilute hydrochloric acid The acid extract isolation through ether in the normal manner gave an oil which was chromatographed as alumina (200g.) Elution with progressively graded mixtures of light petroleum and ether

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

実験手順: A solution of 3-dimethylamino-1,1-diphenyl-propan-2-ol (2 55g) 4-diethylaminobutyric acid hydrochloride (1 95g.) and dicyclohexylcarbodiimide (2.1g.) in dichloromethane (50 ml) was stirred at room temperature for 5 days Dicyclohexylurea was filtered off and the filtrate concentrated. The residue was dissolved in dilute hydrochloric acid and ether. The acid extract was basified; isolation through ether in the normal manner gave an oil which was chromatographed as alumina (200g.). Elution with progressively graded mixtures of light petroleum and ether gave the 4-diethylaminobutyrate of 3-dimethylamino-1,1-diphenyl-propan-2-ol isolated as the dihydrochloride (41%) as a glass was filtered off the filtrate concentrated The residue was dissolved in dilute hydrochloric acid The acid extract isolation through ether in the normal manner gave an oil which was chromatographed as alumina (200g.) Elution with progressively graded mixtures of light petroleum and ether

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

実験手順: 7-n-pentyl-4-[1-(2-naphthylmethyl)-1,2,5,6-tetrahydropyrid-4-yl]-2,2-dimethylchroman-5-ol monohydrate (4.57g., prepared as described in Examples 2 and 3), 4-diethylaminobutyric acid hydrochloride (1.96g.) and dicyclohexylcarbodiimide (2.10g.) were dissolved together in dry dichloromethane (150ml.) and the solution was stirred for 5 days at ambient temperature. The resulting precipitate of dicyclohexylurea was removed by filtration and the filtrate was evaporated to dryness in vacuo. The residual amorphous foam was dissolved in the minimum of ethanol and dry ether was added causing an off-white solid to be precipitated. This solid (2.90g.) was filtered off and the filtrate was treated with ethereal hydrogen chloride to give another off-white precipitate (2.86g.) which was collected by filtration,. These two solids were combined and recrystallised from ethanol-ether to yield the desired 4-diethylaminobutyrate dihydrochloride as hygroscopic, off-white microcrystals (3.79g.), mp 96° C upwards (vague). The resulting precipitate of dicyclohexylurea was removed by filtration the filtrate was evaporated to dryness in vacuo The residual amorphous foam was dissolved in the minimum of ethanol and dry ether was added to be precipitated This solid (2.90g.) was filtered off the filtrate was treated with ethereal hydrogen chloride to give another off-white precipitate (2.86g.) which was collected by filtration recrystallised from ethanol-ether

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

実験手順: A solution of 3-dimethylamino-1,1-diphenyl-propan-2-ol (2.55 g.), 4-diethylaminobutyric acid hydrochloride (1.95 g.) and dicyclohexylcarbodiimide (2.1 g.) in dichloromethane (50 ml.) was stirred at room temperature for 5 days. Dicyclohexylurea was filtered off and the filtrate concentrated. The residue was dissolved in dilute hydrochloric acid and ether. The acid extract was basified; isolation through ether in the normal manner gave an oil which was chromatographed as alumina (200 g.). Elution with progressively graded mixtures of light petroleum and ether gave the 4-diethylaminobutyrate of 3-dimethylamino-1,1-diphenyl-propan-2-ol isolated as the dihydrochloride (41%) as a glass. Dicyclohexylurea was filtered off the filtrate concentrated The residue was dissolved in dilute hydrochloric acid The acid extract isolation through ether in the normal manner gave an oil which was chromatographed as alumina (200 g.) Elution with progressively graded mixtures of light petroleum and ether

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

実験手順: A solution of 3-dimethylamino-1,1-diphenyl-propan-2-ol (2 55g), 4-diethylaminobutyric acid hydrochloride (1 95g) and dicyclohexylcarbodiimide (2 1g) in dichloromethane (50 ml) was stirred at room temperature for 5 days. Dicyclohexylurea was filtered off and the filtrate concentrated. The residue was dissolved in dilute hydrochloric acid and ether. The acid extract was basified; isolation through ether in the normal manner gave an oil which was chromatographed as alumina (200g.). Elution with progressively graded mixtures of light petroleum and ether gave the 4-diethylaminobutyrate of 3-dimethylamino-1,1-diphenyl-propan-2-ol isolated as the dihydrochloride (41%) as a glass. Dicyclohexylurea was filtered off the filtrate concentrated The residue was dissolved in dilute hydrochloric acid The acid extract isolation through ether in the normal manner gave an oil which was chromatographed as alumina (200g.) Elution with progressively graded mixtures of light petroleum and ether

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

実験手順: 7-n-pentyl-4-[1-(2-naphthylmethyl)-1,2,5,6-tetrahydropyrid-4-yl]-2,2-dimethylchroman-5-ol monohydrate (4.57g., prepared as described in Examples 2 and 3), 4-diethylaminobutyric acid hydrochloride (1.96g.) and dicyclohexylcarbodiimide (2.10g.) were dissolved together in dry dichloromethane (150 ml.) and the solution was stirred for 5 days at ambient temperature. The resulting precipitate of dicyclohexylurea was removed by filtration and the filtrate was evaporated to dryness in vacuo. The residual amorphous foam was dissolved in the minimum of ethanol and dry ether was added causing an off-white solid to be precipitated. This solid (2.90g.) was filtered off and the filtrate was treated with ethereal hydrogen chloride to give another off-white precipitate (2.86g.) which was collected by filtration. These two solids were combined and recrystallised from ethanol-ether to yield the desired 4-diethylaminobutyrate dihydrochloride as hygroscopic, off-white microcrystals (3.79g.), mp 96°C upwards (vague). The resulting precipitate of dicyclohexylurea was removed by filtration the filtrate was evaporated to dryness in vacuo The residual amorphous foam was dissolved in the minimum of ethanol and dry ether was added to be precipitated This solid (2.90g.) was filtered off the filtrate was treated with ethereal hydrogen chloride to give another off-white precipitate (2.86g.) which was collected by filtration recrystallised from ethanol-ether

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

実験手順: 0.5 g. (1.39 mmole) of 1,2-dihydro-4,4-dimethyl-9-hydroxy-7-(3-methyl-2-octyl)-4H-thieno[2,3-c][1]benzopyran, 0.31 g. (1.50 mmole; Aldrich Chemical Co.) of dicyclohexylcarbodiimide and 0.272 g. (1.39 mmole) of 4-diethylaminobutyric acid hydrochloride (F. F. Blicke, W. B. Wright, Jr., and M. R. Zienty, J. Amer. Chem. Soc., 63 2488 (1941)) were combined in 30 ml. of methylene chloride and stirred at room temperature for 4 hours. The insoluble by-product of dicyclohexylurea was separated by filtration and the methylene chloride was removed on a rotary evaporator. Attempts to crystallize the material were unsuccessful and 400 mg. (53%) of dark brown residue was obtained. The structure was confirmed by the IR and NMR spectra; and TLC gave Rf 0.5 in 5% MeOH/CHCl3. The acid addition salt may be converted to the free base form by methods well known in the art, and the resulting free base form may then be reacted with another suitable acid to form a different acid addition salt. The insoluble by-product of dicyclohexylurea was separated by filtration the methylene chloride was removed on a rotary evaporator to crystallize the material

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

実験手順: A solution of 3-dimethylamino-1,1-diphenyl-propan-2-ol (2 55g), 4-diethylaminobutyric acid hydrochloride (1 95g) and dicyclohexylcarbodiimide (2 1g) in dichloromethane (50 ml) was stirred at room temperature for 5 days Dicyclohexylurea was filtered off and the filtrate concentrated. The residue was dissolved in dilute hydrochloric acid and ether. The acid extract was basified; isolation through ether in the normal manner gave an oil which was chromatographed as alumina (200g.). Elution with progressively graded mixtures of light petroleum and ether gave the 4-diethylaminobutyrate of 3-dimethylamino-1,1-diphenyl-propan-2-ol isolated as the dihydrochloride (41%) as a glass. was filtered off the filtrate concentrated The residue was dissolved in dilute hydrochloric acid The acid extract isolation through ether in the normal manner gave an oil which was chromatographed as alumina (200g.) Elution with progressively graded mixtures of light petroleum and ether

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

実験手順: A solution of 10.0 g. (0.026 mol.) of 1,3-bis(2-cyano-5-trifluoromethylphenyl)triazene, 6.0 g. (0.029 mol.) of N,N-dicyclohexylcarbodiimide and 5.1 g. (0.026 mol.) of 4-diethylaminobutyric acid hydrochloride in 800 ml. of methylene chloride is stirred at 25° for 12 hours. The reaction mixture is filtered and the filtrate is concentrated under reduced pressure to give a residue which is washed with ether and recrystallized from benzene to give 3-[4-(N,N-diethylamino)butyryl]-1,3-bis(2-cyano-5-trifluoromethylphenyl)-triazene hydrochloride. The reaction mixture is filtered the filtrate is concentrated under reduced pressure to give a residue which is washed with ether recrystallized from benzene

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

実験手順: A solution of 3-dimethylamino-1,1-diphenyl-propan-2-ol (2 55g) 4-diethylaminobutyric acid hydrochloride (1 95g.) and dicyclohexylcarbodiimide (2.1g.) in dichloromethane (50 ml) was stirred at room temperature for 5 days Dicyclohexylurea was filtered off and the filtrate concentrated. The residue was dissolved in dilute hydrochloric acid and ether. The acid extract was basified; isolation through ether in the normal manner gave an oil which was chromatographed as alumina (200g.). Elution with progressively graded mixtures of light petroleum and ether gave the 4-diethylaminobutyrate of 3-dimethylamino-1,1-diphenyl-propan-2-ol isolated as the dihydrochloride (41%) as a glass was filtered off the filtrate concentrated The residue was dissolved in dilute hydrochloric acid The acid extract isolation through ether in the normal manner gave an oil which was chromatographed as alumina (200g.) Elution with progressively graded mixtures of light petroleum and ether

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

実験手順: 7-n-pentyl-4-[1-(2-naphthylmethyl)-1,2,5,6-tetrahydropyrid-4-yl]-2,2-dimethylchroman-5-ol monohydrate (4.57g., prepared as described in Examples 2 and 3), 4-diethylaminobutyric acid hydrochloride (1.96g.) and dicyclohexylcarbodiimide (2.10g.) were dissolved together in dry dichloromethane (150ml.) and the solution was stirred for 5 days at ambient temperature. The resulting precipitate of dicyclohexylurea was removed by filtration and the filtrate was evaporated to dryness in vacuo. The residual amorphous foam was dissolved in the minimum of ethanol and dry ether was added causing an off-white solid to be precipitated. This solid (2.90g.) was filtered off and the filtrate was treated with ethereal hydrogen chloride to give another off-white precipitate (2.86g.) which was collected by filtration,. These two solids were combined and recrystallised from ethanol-ether to yield the desired 4-diethylaminobutyrate dihydrochloride as hygroscopic, off-white microcrystals (3.79g.), mp 96° C upwards (vague). The resulting precipitate of dicyclohexylurea was removed by filtration the filtrate was evaporated to dryness in vacuo The residual amorphous foam was dissolved in the minimum of ethanol and dry ether was added to be precipitated This solid (2.90g.) was filtered off the filtrate was treated with ethereal hydrogen chloride to give another off-white precipitate (2.86g.) which was collected by filtration recrystallised from ethanol-ether

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

実験手順: A solution of 3-dimethylamino-1,1-diphenyl-propan-2-ol (2.55 g.), 4-diethylaminobutyric acid hydrochloride (1.95 g.) and dicyclohexylcarbodiimide (2.1 g.) in dichloromethane (50 ml.) was stirred at room temperature for 5 days. Dicyclohexylurea was filtered off and the filtrate concentrated. The residue was dissolved in dilute hydrochloric acid and ether. The acid extract was basified; isolation through ether in the normal manner gave an oil which was chromatographed as alumina (200 g.). Elution with progressively graded mixtures of light petroleum and ether gave the 4-diethylaminobutyrate of 3-dimethylamino-1,1-diphenyl-propan-2-ol isolated as the dihydrochloride (41%) as a glass. Dicyclohexylurea was filtered off the filtrate concentrated The residue was dissolved in dilute hydrochloric acid The acid extract isolation through ether in the normal manner gave an oil which was chromatographed as alumina (200 g.) Elution with progressively graded mixtures of light petroleum and ether