N-dichlorophosphanyl-N-propan-2-ylpropan-2-amine

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 300 ml abs. ether, 81 ml anhydrous pyridine and 87.5 ml PCl3 (1 Mol) are pre-cooled with stirring to -70° C. in a 2 l three-neck, round-bottomed flask with a 500 ml dropping funnel, KPG stirrer, thermometer and acetone/dry ice bath. 142 ml diisopropylamine (1 Mol) in 250 ml abs. ether are added dropwise to it within 2 hours and the temperature is maintained at ca -60 to -65° C. After completing the addition, the thickened pulpy reaction mixture is allowed to reach room temperature and is diluted with about 600 ml abs. ether to make it more easily stirrable. After a further 3 hours stirring at room temperature the precipitate which forms is aspirated over a glass filter and washed several times with ether. After drawing off the ether at normal pressure, it is freed of unreacted PCl3, diisopropylamine and pyridine in a water-jet vacuum and then the remaining oil is fractionally distilled under an oil-pump vacuum (Kp 46° C./0.35 Torr). 73.4 g of the phosphane is obtained which corresponds to 36% of the theoretical yield. the temperature is maintained at ca -60 to -65° C the addition the thickened pulpy reaction mixture to reach room temperature is diluted with about 600 ml abs After a further 3 hours stirring at room temperature the precipitate which filter washed several times with ether the remaining oil is fractionally distilled under an oil-pump vacuum (Kp 46° C./0.35 Torr)

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 300 ml abs. ether, 81 ml anhydrous pyridine and 87.5 ml PCl3 (1 Mol) are pre-cooled with stirring to -70° C. in a 2 l three-neck, round-bottomed flask with a 500 ml dropping funnel, KPG stirrer, thermometer and acetone/dry ice bath. 142 ml diisopropylamine (1 Mol) in 250 ml abs. ether are added dropwise to it within 2 hours and the temperature is maintained at ca -60 to -65° C. After completing the addition, the thickened pulpy reaction mixture is allowed to reach room temperature and is diluted with about 600 ml abs. ether to make it more easily stirrable. After a further 3 hours stirring at room temperature the precipitate which forms is aspirated over a glass filter and washed several times with ether. After drawing off the ether at normal pressure, it is freed of unreacted PCl3, diisopropylamine and pyridine in a water-jet vacuum and then the remaining oil is fractionally distilled under an oil-pump vacuum (Kp 46° C./0.35 Torr). 73.4 g of the phosphane is obtained which corresponds to 36% of the theoretical yield. the temperature is maintained at ca -60 to -65° C the addition the thickened pulpy reaction mixture to reach room temperature is diluted with about 600 ml abs After a further 3 hours stirring at room temperature the precipitate which filter washed several times with ether the remaining oil is fractionally distilled under an oil-pump vacuum (Kp 46° C./0.35 Torr)

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

実験手順: FIG. 15 illustrates the synthesis of bifunctional diphosphitylating, triphosphitylating, and tetraphosphitylating reagents (66, 69, 72). For the preparation of 66, phosphorus trichloride (21, 875 μL, 10 mmol) and diisopropylethylamine (1,747 μL, 10 mmol) were added to anhydrous THF. Diisopropylamine (1,400 μL, 10 mmol) was added dropwise in 10 min to the solution mixture and the mixture was stirred for 45 min at 0° C. to yield diisopropylphosphoramidodichloridite (29). Then 3-hydroxypropionitrile (22, 683 μL, 10 mmol) and diisopropylethylamine (1,747 μL, 10 mmol) were added dropwise to the solution of 29 in anhydrous THF during 10 min period. The stirring was continued for 25 min at 0° C. to afford 2-cyanoethyl diisopropylphosphoramidochloridite (24). Water (180 μL, 10 mmol) and diisopropylethylamine (1,747 μL, 10 mmol) were added dropwise in 10 min period to the solution. The mixture was stirred for 10 min at 0° C. to yield 2-cyanoethyl diisopropylamine hydroxyphosphite (25). Then 29 (1 eq, 10 mmol) that was prepared at the same time in a separate reaction vessel, was added dropwise in 10 min period to the solution containing 25. The mixture was stirred for 25 min at 0° C. to yield diisopropylphosphoramidochloridite-O-2-cyanoethyl diisopropylphosphoramidite 66 (bifunctional diphosphitylating reagent). The reaction mixture containing diphosphitylating reagent 66 was immediately used in coupling reactions with polymer-bound p-acetoxybenzyl alcohol 78. Further stability studies on 66 using mass spectrometry methods showed that the compound remained stable after 2 months storage at −20° C.

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

実験手順: Bis-(N,N-Diisopropylamino) chlorophosphine, 10 grams (37 mmols), was dissolved in 500 ml of anhydrous acetonitrile. Phosphorus trichloride, 5.16 grams (37 mmols), was added to the solution and the reaction was allowed to stir over-night at room temperature. The reaction was assayed for completion by 31P NMR of an aliquot of the reaction using an external lock. Complete conversion of the starting material at δ 134 ppm to the product at δ 165 ppm was observed. The solvent was evaporated from the reaction mixture on a rotary evaporator and the resulting oil distilled under vacuum yielding 5.7 grams of product (81% yield). The solvent was evaporated from the reaction mixture on a rotary evaporator the resulting oil distilled under vacuum

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

実験手順: FIG. 15 illustrates the synthesis of bifunctional diphosphitylating, triphosphitylating, and tetraphosphitylating reagents (66, 69, 72). For the preparation of 66, phosphorus trichloride (21, 875 μL, 10 mmol) and diisopropylethylamine (1,747 μL, 10 mmol) were added to anhydrous THF. Diisopropylamine (1,400 μL, 10 mmol) was added dropwise in 10 min to the solution mixture and the mixture was stirred for 45 min at 0° C. to yield diisopropylphosphoramidodichloridite (29). Then 3-hydroxypropionitrile (22, 683 μL, 10 mmol) and diisopropylethylamine (1,747 μL, 10 mmol) were added dropwise to the solution of 29 in anhydrous THF during 10 min period. The stirring was continued for 25 min at 0° C. to afford 2-cyanoethyl diisopropylphosphoramidochloridite (24). Water (180 μL, 10 mmol) and diisopropylethylamine (1,747 μL, 10 mmol) were added dropwise in 10 min period to the solution. The mixture was stirred for 10 min at 0° C. to yield 2-cyanoethyl diisopropylamine hydroxyphosphite (25). Then 29 (1 eq, 10 mmol) that was prepared at the same time in a separate reaction vessel, was added dropwise in 10 min period to the solution containing 25. The mixture was stirred for 25 min at 0° C. to yield diisopropylphosphoramidochloridite-O-2-cyanoethyl diisopropylphosphoramidite 66 (bifunctional diphosphitylating reagent). The reaction mixture containing diphosphitylating reagent 66 was immediately used in coupling reactions with polymer-bound p-acetoxybenzyl alcohol 78. Further stability studies on 66 using mass spectrometry methods showed that the compound remained stable after 2 months storage at −20° C.

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

実験手順: Bis-(N,N-Diisopropylamino) chlorophosphine, 10 grams (37 mmols), was dissolved in 500 ml of anhydrous acetonitrile. Phosphorus trichloride, 5.16 grams (37 mmols), was added to the solution and the reaction was allowed to stir over-night at room temperature. The reaction was assayed for completion by 31P NMR of an aliquot of the reaction using an external lock. Complete conversion of the starting material at δ 134 ppm to the product at δ 165 ppm was observed. The solvent was evaporated from the reaction mixture on a rotary evaporator and the resulting oil distilled under vacuum yielding 5.7 grams of product (81% yield). The solvent was evaporated from the reaction mixture on a rotary evaporator the resulting oil distilled under vacuum

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

実験手順: Bis-(N,N-Diisopropylamino)chlorophosphine, 10 grams (37 mmols), was dissolved in 500 ml of anhydrous acetonitrile. Phosphorus trichloride, 5.16 grams (37 mmols), was added to the solution and the reaction was allowed to stir over-night at room temperature. The reaction was assayed for completion by 31P NMR of an aliquot of the reaction using an external lock. Complete conversion of the starting material at δ134 ppm to the product at δ165 ppm was observed. The solvent was evaporated from the reaction mixture on a rotary evaporator and the resulting oil distilled under vacuum yielding 5.7 grams of product (81% yield). The solvent was evaporated from the reaction mixture on a rotary evaporator the resulting oil distilled under vacuum

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 300 ml abs. ether, 81 ml anhydrous pyridine and 87.5 ml PCl3 (1 Mol) are pre-cooled with stirring to -70° C. in a 2 l three-neck, round-bottomed flask with a 500 ml dropping funnel, KPG stirrer, thermometer and acetone/dry ice bath. 142 ml diisopropylamine (1 Mol) in 250 ml abs. ether are added dropwise to it within 2 hours and the temperature is maintained at ca -60° to -65° C. After completing the addition, the thickened pulpy reaction mixture is allowed to reach room temperature and is diluted with about 600 ml abs. ether to make it more easily stirrable. After a further 3 hours stirring at room temperature the precipitate which forms is aspirated over a glass filter and washed several times with ether. After drawing off the ether at normal pressure, it is freed of unreacted PCl3, diisopropylamine and pyridine in a water-jet vacuum and then the remaining oil is fractionally distilled under an oil-pump vacuum (Kp 46° C./0.35 Torr). 73.4 g of the phosphane is obtained which corresponds to 36% of the theoretical yield. the temperature is maintained at ca -60° to -65° C the addition the thickened pulpy reaction mixture to reach room temperature is diluted with about 600 ml abs After a further 3 hours stirring at room temperature the precipitate which filter washed several times with ether the remaining oil is fractionally distilled under an oil-pump vacuum (Kp 46° C./0.35 Torr)

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

実験手順: Bis-(N,N-Diisopropylamino) chlorophosphine, 10 grams (37 mmols), was dissolved in 500 ml of anhydrous acetonitrile. Phosphorus trichloride, 5.16 grams (37 mmols), was added to the solution and the reaction was allowed to stir over-night at room temperature. The reaction was assayed for completion by 31 P NMR of an aliquot of the reaction using an external lock. Complete conversion of the starting material at δ 134 ppm to the product at δ 165 ppm was observed. The solvent was evaporated from the reaction mixture on a rotary evaporator and the resulting oil distilled under vacuum yielding 5.7 grams of product (81% yield). The solvent was evaporated from the reaction mixture on a rotary evaporator the resulting oil distilled under vacuum

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

実験手順: Bis-(N,N-Diisopropylamino)chlorophosphine, 10 grams (37 mmols), was dissolved in 500 ml of anhydrous acetonitrile. Phosphorus trichloride, 5.16 grams (37 mmols), was added to the solution and the reaction was allowed to stir over-night at room temperature. The reaction was assayed for completion by 31P NMR of an aliquot of the reaction using an external lock. Complete conversion of the starting material at δ 134 ppm to the product at δ 165 ppm was observed. The solvent was evaporated from the reaction mixture on a rotary evaporator and the resulting oil distilled under vacuum yielding 5.7 grams of product (81% yield). The solvent was evaporated from the reaction mixture on a rotary evaporator the resulting oil distilled under vacuum

反応条件: temp:-1.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of diisopropylphosphoramidous dichloride (10.8 g 50.78 mmoles) in Et2O (53 mL) in 250 mL three neck flask equipped with a temperature probe and addition funnel was cooled to 0 to −2° C. under N2. A solution of 2-(trimethylsilyl)ethanol (12.6 g; 106.55 mmoles) and Et3N (15.4 g; 152.19 mmoles) in Et2O (84 mL) was added dropwise over 27-28 minutes to the stirred diisopropyl-phosphoramidous dichloride solution. A mild exotherm (+1-2° C.) accompanied the formation of a thick white suspension. After stirring overnight at 20° C., the mixture was filtered. The resultant cake was washed twice with 30 mL each of Et2O. The combined filtrates were washed 2×100 mL of saturated aqueous NaHCO3 followed by 40 mL of brine. After drying over MgSO4 and concentrating to dryness under vacuum at room temperature, bis(2-(trimethylsilyl)ethyl) diisopropylphosphoramidite (18.12 g; 49.56 mmoles; 97.60% yield) was obtained as a clear colorless liquid. 1H NMR δ (400 MHz, CDCl3): 3.90-3.78 (m, 4H), 3.77-3.68 (m, 2H), 1.31 (d, J=6.6 Hz, 12H), 1.17-1.12 (m, 4H), 0.15 (s, 18H). 13C NMR δ (100 MHz, CDCl3): δ0.7 (2, d, JC—P=19.1 Hz, 2C), 42.7 (1, d, JC—P=12.7 Hz, 2C), 24.6 (3, d, JC—P=7.6 Hz, 4C), 20.1 (2, d, JC—P=7.6 Hz, 2C), −1.4 (3, 6C). 31P NMR δ (162 MHz, CDCl3): 143.5 (s). LC/MS: m/e (M+H); 4 ml gradient; min retention. A mild exotherm (+1-2° C.) the mixture was filtered The resultant cake was washed twice with 30 mL each of Et2O The combined filtrates were washed 2×100 mL of saturated aqueous NaHCO3 After drying over MgSO4 concentrating to dryness under vacuum at room temperature