heptane-1,7-diol

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: A solution of 1,7-heptandiol (44 mmol) in THF (15 mL) is cooled to 0° C. and treated with sodium hydride (44 mmol) followed by tert-butyldimethylsilyl chloride (44 mmol). The reaction mixture is stirred at room temperature overnight. Concentration in vacuo and flash chromatography affords 7-trimethylsiloxy-1-heptanol. To a solution of 7-trimethylsiloxy-1-heptanol (11.6 mmol) in dry dichloromethane (50 mL) is added 2,6-di-tert-butyl-4-methylpyridine (4.6 g, 22.2 mmol) and triflic anhydride (3.7 mL, 22.2 mmol) at 0° C. The reaction is stirred at room temperature for 20 min, poured into water, and extracted with dichloromethane. The combined extracts are dried over anhydrous sodium sulfate and concentrated in vacuo and to afford 7-trimethylsiloxy-1-heptyl triflate (50) which is used without further purification. Concentration in vacuo and flash chromatography

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

実験手順: Diethyl azodicarboxylate (0.94 g) was added to a mixture of 3-azabicyclo[3.1.0]hexane-2,4-dione (0.5 g), 1,7-heptanediol (2.46 g), triphenylphosphine (1.42 g) and 4 angstrom sieves (1.5 g) in dry tetrahydrofuran (10 ml) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 2 days and was then filtered. The solids were washed with ethyl acetate (2×50 ml) and the combined filtrates were evaporated in vacuo. The residue was purified by chromatography on silica using 60-70% ethyl acetate/hexane as eluant, followed by kugelrohr distillation (b.p. 200-220° C. @ 1 mmHg) to give the subtitle compound as a viscous oil. was then filtered The solids were washed with ethyl acetate (2×50 ml) the combined filtrates were evaporated in vacuo The residue was purified by chromatography on silica using 60-70% ethyl acetate/hexane as eluant followed by kugelrohr distillation (b.p. 200-220° C. @ 1 mmHg)

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

実験手順: The title compound was obtained using the following procedure: The sulfamoyl chloride in acetonitrile solution prepared in (a) was reacted as in Example 12 with 10.5 g (0.0755 mole) of 1,7-heptanediol (95%), 30.3 g (0.300 mole) of triethylamine in 100 ml additional acetonitrile followed by using extracting, washing and concentration procedures of Example 12 through the first evaporation. The viscous residue which solidified on standing was purified by high pressure liquid chromatography using the Waters Associates® Prep LC/System 500A with Prep Pak 500 ® silica. Eluting solvent used was 10:1 mixture methylene chloride-acetone at a flow rate of 200 ml/min. Fractions containing the title compound were combined and the solvents were evaporated under reduced pressure to give a viscous oil which solidified on standing. The solid was recrystallized from wet methylene chloride to give 8.2 g (37% yield) of title compound as white solid, mp 88.5°-90.5° C. by using extracting washing concentration procedures of Example 12 through the first evaporation was purified by high pressure liquid chromatography Fractions containing the title compound the solvents were evaporated under reduced pressure to give a viscous oil which The solid was recrystallized from wet methylene chloride

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

実験手順: 3-(7-Decyloxyheptylthio)-propanol (m.p. 28°-32° C.), obtained by reacting heptane-1,7-diol with 1-bromodecane to give 7-decyloxyheptanol, bromination thereof to give 7-decyloxyheptyl bromide, reaction with methyl β-mercaptopropionate to give methyl β-(7-decyloxyheptylthio)-propionate and reduction with lithium aluminium hydride, is reacted in the manner described in Example 20C to give the desired choline ester in a yield of 17% of theory. The water-soluble, white crystals sinter at 53° C. and melt at 224° C.

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

実験手順: A solution of 1,7-heptandiol (44 mmol) in THF (15 mL) is cooled to 0° C. and treated with sodium hydride (44 mmol) followed by tert-butyldimethylsilyl chloride (44 mmol). The reaction mixture is stirred at room temperature overnight. Concentration in vacuo and flash chromatography affords 7-trimethylsiloxy-1-heptanol . To a solution of 7-trimethylsiloxy-1-heptanol (11.6 mmol) in dry dichloromethane (50 mL) is added 2,6-di-tert-butyl-4-methylpyridine (4.6 g, 22.2 mmol) and triflic anhydride (3.7 mL, 22.2 mmol) at 0° C. The reaction is stirred at room temperature for 20 min, poured into water, and extracted with dichloromethane. The combined extracts are dried over anhydrous sodium sulfate and concentrated in vacuo and to afford 7-trimethylsiloxy-1-heptyl triflate (50) which is used without further purification. Concentration in vacuo and flash chromatography

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

実験手順: A solution of 1,7-heptandiol (44 mmol) in THF (15 mL) is cooled to 0° C. and treated with sodium hydride (44 mmol) followed by tert-butyldimethylsilyl chloride (44 mmol). The reaction mixture is stirred at room temperature overnight. Concentration in vacuo and flash chromatography affords 7-trimethylsiloxy-1-heptanol . To a solution of 7-trimethylsiloxy-1-heptanol (11.6 mmol) in dry dichloromethane (50 mL) is added 2,6-di-tert-butyl-4-methylpyridine (4.6 g, 22.2 mmol) and triflic anhydride (3.7 mL, 22.2 mmol) at 0° C. The reaction is stirred at room temperature for 20 min, poured into water, and extracted with dichloromethane. The combined extracts are dried over anhydrous sodium sulfate and concentrated in vacuo and to afford 7-trimethylsiloxy-1-heptyl triflate (50) which is used without further purification. Concentration in vacuo and flash chromatography

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

実験手順: Heptane-1,7-diol (36.0 g, 272 mmol; Alfa Aesar) and aq. 48% HBr (38 mL) were heated under reflux in benzene (400 mL) with water removal using a Dean-Stark apparatus. After 12 h, all volatiles were removed in vacuo and the residue was purified by SiO2 column chromatography using a gradient of 10-30% EtOAc/hexanes as eluent to give 7-bromoheptan-1-ol (26.22 g, 62%) as colorless oil. TLC: 50% EtOAc/hexanes, Rf≈0.4; 1H NMR (400 MHz, CDCl3) δ 3.61 (t, 2H, J=7.1 Hz), 3.39 (t, 2H, J=6.8 Hz), 1.80-1.88 (m, 2H), 1.52-1.58 (m, 2H), 1.30-1.46 (m, 6H). all volatiles were removed in vacuo the residue was purified by SiO2 column chromatography

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

実験手順: A solution of 1,7-heptandiol (44 mmol) in THF (15 mL) is cooled to 0° C. and treated with sodium hydride (44 mmol) followed by tert-butyldimethylsilyl chloride (44 mmol). The reaction mixture is stirred at room temperature overnight. Concentration in vacuo and flash chromatography affords 7-trimethylsiloxy-1-heptanol. To a solution of 7-trimethylsiloxy-1-heptanol (11.6 mmol) in dry dichloromethane (50 mL) is added 2,6-di-tert-butyl-4-methylpyridine (4.6 g, 22.2 mmol) and triflic anhydride (3.7 mL, 22.2 mmol) at 0° C. The reaction is stirred at room temperature for 20 min, poured into water, and extracted with dichloromethane. The combined extracts are dried over anhydrous sodium sulfate and concentrated in vacuo and to afford 7-trimethylsiloxy-1-heptyl triflate (50) which is used without further purification. Concentration in vacuo and flash chromatography

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

実験手順: Diethyl azodicarboxylate (0.94 g) was added to a mixture of 3-azabicyclo[3.1.0]hexane-2,4-dione (0.5 g), 1,7-heptanediol (2.46 g), triphenylphosphine (1.42 g) and 4 angstrom sieves (1.5 g) in dry tetrahydrofuran (10 ml) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 2 days and was then filtered. The solids were washed with ethyl acetate (2×50 ml) and the combined filtrates were evaporated in vacuo. The residue was purified by chromatography on silica using 60-70% ethyl acetate/hexane as eluant, followed by kugelrohr distillation (b.p. 200-220° C. @ 1 mmHg) to give the subtitle compound as a viscous oil. was then filtered The solids were washed with ethyl acetate (2×50 ml) the combined filtrates were evaporated in vacuo The residue was purified by chromatography on silica using 60-70% ethyl acetate/hexane as eluant followed by kugelrohr distillation (b.p. 200-220° C. @ 1 mmHg)

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

実験手順: The title compound was obtained using the following procedure: The sulfamoyl chloride in acetonitrile solution prepared in (a) was reacted as in Example 12 with 10.5 g (0.0755 mole) of 1,7-heptanediol (95%), 30.3 g (0.300 mole) of triethylamine in 100 ml additional acetonitrile followed by using extracting, washing and concentration procedures of Example 12 through the first evaporation. The viscous residue which solidified on standing was purified by high pressure liquid chromatography using the Waters Associates® Prep LC/System 500A with Prep Pak 500 ® silica. Eluting solvent used was 10:1 mixture methylene chloride-acetone at a flow rate of 200 ml/min. Fractions containing the title compound were combined and the solvents were evaporated under reduced pressure to give a viscous oil which solidified on standing. The solid was recrystallized from wet methylene chloride to give 8.2 g (37% yield) of title compound as white solid, mp 88.5°-90.5° C. by using extracting washing concentration procedures of Example 12 through the first evaporation was purified by high pressure liquid chromatography Fractions containing the title compound the solvents were evaporated under reduced pressure to give a viscous oil which The solid was recrystallized from wet methylene chloride

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

実験手順: The title compound was obtained using the following procedure: The sulfamoyl chloride in acetonitrile solution prepared in (a) was reacted as in Example 12 with 10.5 g (0.0755 mole) of 1,7-heptanediol (95%), 30.3 g (0.300 mole) of triethylamine in 100 ml additional acetonitrile followed by using extracting, washing and concentration procedures of Example 12 through the first evaporation. The viscous residue which solidified on standing was purified by high pressure liquid chromatography using the Waters Associates® Prep LC/System 500A with Prep Pak 500 ® silica. Eluting solvent used was 10:1 mixture methylene chloride-acetone at a flow rate of 200 ml/min. Fractions containing the title compound were combined and the solvents were evaporated under reduced pressure to give a viscous oil which solidified on standing. The solid was recrystallized from wet methylene chloride to give 8.2 g (37% yield) of title compound as white solid, mp 88.5°-90.5° C. by using extracting washing concentration procedures of Example 12 through the first evaporation was purified by high pressure liquid chromatography Fractions containing the title compound the solvents were evaporated under reduced pressure to give a viscous oil which The solid was recrystallized from wet methylene chloride