magnesium;propan-2-olate

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9-(2-Hydroxyethyl)adenine (HEA) (20.0 g, 0.112 mol) was suspended in DMF (125 ml) and heated to 80° C. Magnesium isopropoxide (11.2 g, 0.0784 mol), or alternatively magnesium t-butoxide, was added to the mixture followed by diethyl p-toluenesulfonyloxymethylphosphonate (66.0 g, 0.162 mol) over one hour. The mixture was stirred at 80° C. for 7 hours. 30 ml of volatiles were removed via vacuum distillation and the reaction was recharged with 30 ml of fresh DMF. After cooling to room temperature, bromotrimethylsilane (69.6 g, 0.450 mol) was added and the mixture heated to 80° C. for 6 hours. The reaction was concentrated to yield a thick gum. The gum was dissolved into 360 ml water, extracted with 120 ml dichloromethane, adjusted to pH 3.2 with sodium hydroxide, and the resulting slurry stirred at room temperature overnight. The slurry was cooled to 4° C. for one hour. The solids were isolated by filtration, washed with water (2×), and dried in vacuo at 56° C. to yield 20 g (65.4%) of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) as a white solid. Mp:>200° C. dec. 1H NMR (D2O) δ 3.49 (t, 2H); 3.94 (t, 2H); 4.39 (t, 2H); 8.13 (s, 1H); 8.22 (s, 1H). 30 ml of volatiles were removed via vacuum distillation After cooling to room temperature the mixture heated to 80° C. for 6 hours The reaction was concentrated to yield a thick gum extracted with 120 ml dichloromethane the resulting slurry stirred at room temperature overnight The slurry was cooled to 4° C. for one hour The solids were isolated by filtration washed with water (2×) dried in vacuo at 56° C.

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Adenine to PMEA using Magnesium Isopropoxide. To a suspension of adenine (16.8 g, 0.124 mol) in DMF (41.9 ml) was added ethylene carbonate (12.1 g, 0.137 mol) and sodium hydroxide (.100 g, 0.0025 mol). The mixture was heated at 130° C. overnight. The reaction was cooled to below 50° C. and toluene (62.1 ml) was added. The slurry was further cooled to 5° C. for 2 hours, filtered, and rinsed with toluene (2×). The wet solid was dried in vacuo at 65° C. to yield 20.0 g (90%) of 9-(2-hydroxyethyl)adenine as an off-white solid. Mp: 238-240° C. The reaction was cooled to below 50° C. The slurry was further cooled to 5° C. for 2 hours filtered rinsed with toluene (2×) The wet solid was dried in vacuo at 65° C.

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9-(2-Hydroxyethyl)adenine (HEA) (20.0 g, 0.112 mol) was suspended in DMF (125 ml) and heated to 80° C. Magnesium isopropoxide (11.2 g, 0.0784 mol), or alternatively magnesium t-butoxide, was added to the mixture followed by diethyl p-toluenesulfonyloxymethylphosphonate (66.0 g, 0.162 mol) over one hour. The mixture was stirred at 80° C. for 7 hours. 30 ml of volatiles were removed via vacuum distillation and the reaction was recharged with 30 ml of fresh DMF. After cooling to room temperature, bromotrimethylsilane (69.6 g, 0.450 mol) was added and the mixture heated to 80° C. for 6 hours. The reaction was concentrated to yield a thick gum. The gum was dissolved into 360 ml water, extracted with 120 ml dichloromethane, adjusted to pH 3.2 with sodium hydroxide, and the resulting slurry stirred at room temperature overnight. The slurry was cooled to 4° C. for one hour. The solids were isolated by filtration, washed with water (2×), and dried in vacuo at 56° C. to yield 20 g (65.4%) of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) as a white solid. Mp:>200° C. dec. 1H NMR (D2O) δ 3.49 (t, 2H); 3.94 (t, 2H); 4.39 (t, 2H); 8.13 (s, 1H); 8.22 (s, 1H). 30 ml of volatiles were removed via vacuum distillation After cooling to room temperature the mixture heated to 80° C. for 6 hours The reaction was concentrated to yield a thick gum extracted with 120 ml dichloromethane the resulting slurry stirred at room temperature overnight The slurry was cooled to 4° C. for one hour The solids were isolated by filtration washed with water (2×) dried in vacuo at 56° C.

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Adenine to PMEA using Magnesium Isopropoxide. To a suspension of adenine (16.8 g, 0.124 mol) in DMF (41.9 ml) was added ethylene carbonate (12.1 g, 0.137 mol) and sodium hydroxide (.100 g, 0.0025 mol). The mixture was heated at 130° C. overnight. The reaction was cooled to below 50° C. and toluene (62.1 ml) was added. The slurry was further cooled to 5° C. for 2 hours, filtered, and rinsed with toluene (2×). The wet solid was dried in vacuo at 65° C. to yield 20.0 g (90%) of 9-(2-hydroxyethyl)adenine as an off-white solid. Mp: 238-240° C. The reaction was cooled to below 50° C. The slurry was further cooled to 5° C. for 2 hours filtered rinsed with toluene (2×) The wet solid was dried in vacuo at 65° C.

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (R)-9-[2-(hydroxy)propyl]adenine (HPA) (20.0 g, 0.104 mol) was suspended in DMF (44.5 ml) and heated to 65° C. Magnesium t-butoxide (14.2 g, 0.083 mol), or alternatively magnesium isopropoxide, was added to the mixture over one hour followed by diethyl p-toluenesulfonyloxymethylphosphonate (66.0 g, 0.205 mol) over two hours while the temperature was kept at 78° C. The mixture was stirred at 75° C. for 4 hours. After cooling to below 50° C., bromotrimethylsilane (73.9 g, 0.478 mol) was added and the mixture heated to 77° C. for 3 hours. When complete, the reaction was heated to 80° C. and volatiles were removed via atmospheric distillation. The residue was dissolved into water (120 ml) at 50° C. and then extracted with ethyl acetate (101 ml). The pH of the aqueous phase was adjusted to pH 1.1 with sodium hydroxide, seeded with authentic (R)-PMPA, and the pH of the aqueous layer was readjusted to pH 2.1 with sodium hydroxide. The resulting slurry was stirred at room temperature overnight. The slurry was cooled to 4° C. for three hours. The solid was isolated by filtration, washed with water (60 ml), and dried in vacuo at 50° C. to yield 18.9 g (63.5%) of crude (R)-9-[2-(phosphonomethoxy)propyl]adenine (PMPA) as an off-white solid. was kept at 78° C After cooling to below 50° C. the mixture heated to 77° C. for 3 hours When complete, the reaction was heated to 80° C. volatiles were removed via atmospheric distillation The residue was dissolved into water (120 ml) at 50° C. extracted with ethyl acetate (101 ml) The resulting slurry was stirred at room temperature overnight The slurry was cooled to 4° C. for three hours The solid was isolated by filtration washed with water (60 ml) dried in vacuo at 50° C.

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9-(2-Hydroxyethyl)adenine (HEA) (20.0 g, 0.112 mol) was suspended in is DMF (125 ml) and heated to 80° C. Magnesium isopropoxide (11.2 g, 0.0784 mol), or alternatively magnesium t-butoxide, was added to the mixture followed by diethyl p-toluenesulfonyloxymethylphosphonate (66.0 g, 0.162 mol) over one hour. The mixture was stirred at 80° C. for 7 hours. 30 ml of volatiles were removed via vacuum distillation and the reaction was recharged with 30 ml of fresh DMF. After cooling to room temperature, bromotrimethylsilane (69.6 g, 0.450 mol) was added and the mixture heated to 80° C. for 6 hours. The reaction was concentrated to yield a thick gum. The gum was dissolved into 360 ml water, extracted with 120 ml dichloromethane, adjusted to pH 3.2 with sodium hydroxide, and the resulting slurry stirred at room temperature overnight. The slurry was cooled to 4° C. for one hour. The solids were isolated by filtration, washed with water (2×), and dried in vacuo at 56° C. to yield 20 g (65.4%) of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) as a white solid. Mp: >200° C. dec. 1H NMR (D2O) δ 3.49 (t, 2H); 3.94 (t, 2H); 4.39 (t, 2H); 8.13 (s, 1H); 8.22 (s, 1H). 30 ml of volatiles were removed via vacuum distillation After cooling to room temperature the mixture heated to 80° C. for 6 hours The reaction was concentrated to yield a thick gum extracted with 120 ml dichloromethane the resulting slurry stirred at room temperature overnight The slurry was cooled to 4° C. for one hour The solids were isolated by filtration washed with water (2×) dried in vacuo at 56° C.

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Adenine to PMEA using Magnesium Isopropoxide. To a suspension of adenine (16.8 g, 0.124 mol) in DMF (41.9 ml) was added ethylene carbonate (12.1 g, 0.137 mol) and sodium hydroxide (0.100 g, 0.0025 mol). The mixture was heated at 130° C. overnight. The reaction was cooled to below 50° C. and toluene (62.1 ml) was added. The slurry was further cooled to 5° C. for 2 hours, filtered, and rinsed with toluene (2×). The wet solid was dried in vacuo at 65° C. to yield 20.0 g (90%) of 9-(2-hydroxyethyl)adenine as an off-white solid. Mp: 238-240° C. The reaction was cooled to below 50° C. The slurry was further cooled to 5° C. for 2 hours filtered rinsed with toluene (2×) The wet solid was dried in vacuo at 65° C.

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

実験手順: If magnesium isopropanolate, together with e.g., 20 moles % of tetrabutoxy titanium, with respect to the amount of magnesium, and one or two equivalents of decanol, is introduced into an organic solvent, and the mixture is heated, a desirably low-viscosity solution of magnesium isopropanolatedecanolate, and/or of magnesium didecanolate, is formed, from which the liberated isopropanol can now readily be evaporated so as to achieve substantially full completion of the reaction. the mixture is heated

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9-(2-Hydroxyethyl)adenine (HEA) (20.0 g, 0.112 mol) was suspended in DMF (125 ml) and heated to 80° C. Magnesium isopropoxide (11.2 g, 0.0784 mol), or alternatively magnesium t-butoxide, was added to the mixture followed by diethyl p-toluenesulfonyloxymethylphosphonate (66.0 g, 0.162 mol) over one hour. The mixture was stirred at 80° C. for 7 hours. 30 ml of volatiles were removed via vacuum distillation and the reaction was recharged with 30 ml of fresh DMF. After cooling to room temperature, bromotrimethylsilane (69.6 g, 0.450 mol) was added and the mixture heated to 80° C. for 6 hours. The reaction was concentrated to yield a thick gum. The gum was dissolved into 360 ml water, extracted with 120 ml dichloromethane, adjusted to pH 3.2 with sodium hydroxide, and the resulting slurry stirred at room temperature overnight. The slurry was cooled to 4° C. for one hour. The solids were isolated by filtration, washed with water (2×), and dried in vacuo at 56° C. to yield 20 g (65.4%) of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) as a white solid. Mp:>200° C. dec. 1H NMR (D2O) δ 3.49 (t, 2H); 3.94 (t, 2H); 4.39 (t, 2H); 8.13 (s, 1H); 8.22 (s, 1H). 30 ml of volatiles were removed via vacuum distillation After cooling to room temperature the mixture heated to 80° C. for 6 hours The reaction was concentrated to yield a thick gum extracted with 120 ml dichloromethane the resulting slurry stirred at room temperature overnight The slurry was cooled to 4° C. for one hour The solids were isolated by filtration washed with water (2×) dried in vacuo at 56° C.

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Adenine to PMEA using Magnesium Isopropoxide. To a suspension of adenine (16.8 g, 0.124 mol) in DMF (41.9 ml) was added ethylene carbonate (12.1 g, 0.137 mol) and sodium hydroxide (.100 g, 0.0025 mol). The mixture was heated at 130° C. overnight. The reaction was cooled to below 50° C. and toluene (62.1 ml) was added. The slurry was further cooled to 5° C. for 2 hours, filtered, and rinsed with toluene (2×). The wet solid was dried in vacuo at 65° C. to yield 20.0 g (90%) of 9-(2-hydroxyethyl)adenine as an off-white solid. Mp: 238-240° C. The reaction was cooled to below 50° C. The slurry was further cooled to 5° C. for 2 hours filtered rinsed with toluene (2×) The wet solid was dried in vacuo at 65° C.