1-dimethylphosphoryl-4-fluorobenzene

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

実験手順: A sealed pressure flask, flushed with N2, containing a mixture of 3.90 g (22.7 mmol) of 1-(Dimethyl-phosphinoyl)-4-fluoro-benzene and 6.0 g (113.3 mmol) of LiNO2 (for prep see, W. C. Ball and H. H. Abram J. Chem. Soc. 1913, 103, 2130-2134) in 27 mL of DMPU (1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone) was stirred at ambient temperature for 5-10 min (to dissolve fluoro compound) then heated at 190° C. for 3 days. The resulting dark brown solution was cooled to ambient temperature, diluted with 300 mL of brine, then extracted with EtOAc (10×100 mL) until the aqueous layer showed little or no evidence of product by HPLC. The combined organics were dried over MgSO4 and concentrated. The excess DMPU was removed via short-path distillation (120° C./0.3 mm) to provide a semi-solid, which was dissolved in a minimum amount of iPrOH and purified by silica gel flash chromatography (eluted with 5% iPrOH/DCM, then 10% iPrOH/DCM, then 15% iPrOH/DCM) to provide 2.04 g of an yellow solid: 1H NMR (300 MHz, DMSO-d6) δ 8.34 (dd, J=8.7, 1.9 Hz, 2H), 8.07 (dd, J=10.6, 8.8 Hz, 2H), 1.75 (s, 3H), 1.70 (s, 3H). 31P NMR (121 MHz, DMSO-d6) δ 37.89. A sealed pressure flask, flushed with N2 containing then heated at 190° C. for 3 days The resulting dark brown solution was cooled to ambient temperature extracted with EtOAc (10×100 mL) until the aqueous layer The combined organics were dried over MgSO4 concentrated The excess DMPU was removed via short-path distillation (120° C./0.3 mm) to provide a semi-solid, which purified by silica gel flash chromatography ( eluted with 5% iPrOH/DCM

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a cooled (0° C.) flask containing 34.0 mL (2.0 M in Et2O, 68.4 mmol) of 4-fluorophenylmagnesium bromide, under an atmosphere of N2, was added a solution of dimethylphosphinic chloride (3.50 g, 31.1 mmol) in 84 mL of THF, dropwise via cannulation, over 20 min. The green reaction mixture was stirred at 0° C. for 1 h, then quenched at 0° C. with 30 mL of saturated NH4Cl resulting in the formation of a white precipitate. The mixture was concentrated on a rotary evaporator and partitioned between EtOAc (200 mL) and H2O (200 mL), upon which the layers were separated. The aqueous layer was extracted with EtOAc (3×100 mL) and the combined organics washed with brine, then dried over MgSO4 and concentrated. The crude product was purified by silica gel flash chromatography (eluted with 5% MeOHIDCM) to provide 2.08 g of an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ 7.83 (m, 2H), 7.35 (td, J=8.9, 1.7 Hz, 2H), 1.66 (s, 3H), 1.61 (s, 3H). 31P NMR (121 MHz, DMSO-d6) δ 37.186. 19F NMR (282 MHz, DMSO-d6) δ−105.14. quenched at 0° C. with 30 mL of saturated NH4Cl resulting in the formation of a white precipitate The mixture was concentrated on a rotary evaporator partitioned between EtOAc (200 mL) and H2O (200 mL), upon which the layers were separated The aqueous layer was extracted with EtOAc (3×100 mL) the combined organics washed with brine dried over MgSO4 concentrated The crude product was purified by silica gel flash chromatography (eluted with 5% MeOHIDCM)

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

実験手順: A sealed pressure flask, flushed with N2, containing a mixture of 3.90 g (22.7 mmol) of 1-(Dimethyl-phosphinoyl)-4-fluoro-benzene and 6.0 g (113.3 mmol) of LiNO2 (for prep see, W. C. Ball and H. H. Abram J. Chem. Soc. 1913, 103, 2130–2134) in 27 mL of DMPU (1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone) was stirred at ambient temperature for 5–10 min (to dissolve fluoro compound) then heated at 190° C. for 3 days. The resulting dark brown solution was cooled to ambient temperature, diluted with 300 mL of brine, then extracted with EtOAc (10×100 mL) until the aqueous layer showed little or no evidence of product by HPLC. The combined organics were dried over MgSO4 and concentrated. The excess DMPU was removed via short-path distillation (120° C./0.3 mm) to provide a semi-solid, which was dissolved in a minimum amount of iPrOH and purified by silica gel flash chromatography (eluted with 5% iPrOH/DCM, then 10% iPrOH/DCM, then 15% iPrOH/DCM) to provide 2.04 g of an yellow solid: 1H NMR (300 MHz, DMSO-d6) δ 8.34 (dd, J=8.7, 1.9 Hz, 2H), 8.07 (dd, J=10.6, 8.8 Hz, 2H), 1.75 (s, 3H), 1.70 (s, 3H). 31P NMR (121 MHz, DMSO-d6) δ 37.89. A sealed pressure flask, flushed with N2 containing then heated at 190° C. for 3 days The resulting dark brown solution was cooled to ambient temperature extracted with EtOAc (10×100 mL) until the aqueous layer The combined organics were dried over MgSO4 concentrated The excess DMPU was removed via short-path distillation (120° C./0.3 mm) to provide a semi-solid, which purified by silica gel flash chromatography ( eluted with 5% iPrOH/DCM

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

実験手順: A sealed pressure flask, flushed with N2, containing a mixture of 3.90 g (22.7 mmol) of 1-(Dimethyl-phosphinoyl)-4-fluoro-benzene and 6.0 g (113.3 mmol) of LiNO2 (for prep see, W. C. Ball and H. H. Abram J. Chem. Soc. 1913, 103, 2130–2134) in 27 mL of DMPU (1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone) was stirred at ambient temperature for 5–10 min (to dissolve fluoro compound) then heated at 190° C. for 3 days. The resulting dark brown solution was cooled to ambient temperature, diluted with 300 mL of brine, then extracted with EtOAc (10×100 mL) until the aqueous layer showed little or no evidence of product by HPLC. The combined organics were dried over MgSO4 and concentrated. The excess DMPU was removed via short-path distillation (120° C./0.3 mm) to provide a semi-solid, which was dissolved in a minimum amount of iPrOH and purified by silica gel flash chromatography (eluted with 5% iPrOH/DCM, then 10% iPrOH/DCM, then 15% iPrOH/DCM) to provide 2.04 g of an yellow solid: 1H NMR (300 MHz, DMSO-d6) δ 8.34 (dd, J=8.7, 1.9 Hz, 2H), 8.07 (dd, J=10.6, 8.8 Hz, 2H), 1.75 (s, 3H), 1.70 (s, 3H). 31P NMR (121 MHz, DMSO-d6) δ 37.89. A sealed pressure flask, flushed with N2 containing then heated at 190° C. for 3 days The resulting dark brown solution was cooled to ambient temperature extracted with EtOAc (10×100 mL) until the aqueous layer The combined organics were dried over MgSO4 concentrated The excess DMPU was removed via short-path distillation (120° C./0.3 mm) to provide a semi-solid, which purified by silica gel flash chromatography ( eluted with 5% iPrOH/DCM

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a cooled (0° C.) flask containing 34.0 mL (2.0 M in Et2O, 68.4 mmol) of 4-fluorophenylmagnesium bromide, under an atmosphere of N2, was added a solution of dimethylphosphinic chloride (3.50 g, 31.1 mmol) in 84 mL of THF, dropwise via cannulation, over 20 min. The green reaction mixture was stirred at 0° C. for 1 h, then quenched at 0° C. with 30 mL of saturated NH4Cl resulting in the formation of a white precipitate. The mixture was concentrated on a rotary evaporator and partitioned between EtOAc (200 mL) and H2O (200 mL), upon which the layers were separated. The aqueous layer was extracted with EtOAc (3×100 mL) and the combined organics washed with brine, then dried over MgSO4 and concentrated. The crude product was purified by silica gel flash chromatography (eluted with 5% MeOH/DCM) to provide 2.08 g of an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ 7.83 (m, 2H), 7.35 (td, J=8.9, 1.7 Hz, 2H), 1.66 (s, 3H), 1.61 (s, 3H). 31P NMR (121 MHz, DMSO-d6) δ 37.186. 19F NMR (282 MHz, DMSO-d6) δ−105.14. quenched at 0° C. with 30 mL of saturated NH4Cl resulting in the formation of a white precipitate The mixture was concentrated on a rotary evaporator partitioned between EtOAc (200 mL) and H2O (200 mL), upon which the layers were separated The aqueous layer was extracted with EtOAc (3×100 mL) the combined organics washed with brine dried over MgSO4 concentrated The crude product was purified by silica gel flash chromatography (eluted with 5% MeOH/DCM)

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

実験手順: A sealed pressure flask, flushed with N2, containing a mixture of 3.90 g (22.7 mmol) of 1-(Dimethyl-phosphinoyl)-4-fluoro-benzene and 6.0 g (113.3 mmol) of LiNO2 (for prep see, W. C. Ball and H. H. Abram J. Chem. Soc. 1913, 103, 2130-2134) in 27 mL of DMPU (1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone) was stirred at ambient temperature for 5-10 min (to dissolve fluoro compound) then heated at 190° C. for 3 days. The resulting dark brown solution was cooled to ambient temperature, diluted with 300 mL of brine, then extracted with EtOAc (10×100 mL) until the aqueous layer showed little or no evidence of product by HPLC. The combined organics were dried over MgSO4 and concentrated. The excess DMPU was removed via short-path distillation (120° C./0.3 mm) to provide a semi-solid, which was dissolved in a minimum amount of iPrOH and purified by silica gel flash chromatography (eluted with 5% iPrOH/DCM, then 10% iPrOH/DCM, then 15% iPrOH/DCM) to provide 2.04 g of an yellow solid: 1H NMR (300 MHz, DMSO-d6) δ8.34 (dd, J=8.7, 1.9 Hz, 2H), 8.07 (dd, J=10.6, 8.8 Hz, 2H), 1.75 (s, 3H), 1.70 (s, 3H). 31P NMR (121 MHz, DMSO-d6) δ37.89. A sealed pressure flask, flushed with N2 containing then heated at 190° C. for 3 days The resulting dark brown solution was cooled to ambient temperature extracted with EtOAc (10×100 mL) until the aqueous layer The combined organics were dried over MgSO4 concentrated The excess DMPU was removed via short-path distillation (120° C./0.3 mm) to provide a semi-solid, which purified by silica gel flash chromatography ( eluted with 5% iPrOH/DCM

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a cooled (0° C.) flask containing 34.0 mL (2.0 M in Et2O, 68.4 mmol) of 4-fluorophenylmagnesium bromide, under an atmosphere of N2, was added a solution of dimethylphosphinic chloride (3.50 g, 31.1 mmol) in 84 mL of THF, dropwise via cannulation, over 20 min. The green reaction mixture was stirred at 0° C. for 1 h, then quenched at 0° C. with 30 mL of saturated NH4Cl resulting in the formation of a white precipitate. The mixture was concentrated on a rotary evaporator and partitioned between EtOAc (200 mL) and H2O (200 mL), upon which the layers were separated. The aqueous layer was extracted with EtOAc (3×100 mL) and the combined organics washed with brine, then dried over MgSO4 and concentrated. The crude product was purified by silica gel flash chromatography (eluted with 5% MeOH/DCM) to provide 2.08 g of an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ7.83 (m, 2H), 7.35 (td, J=8.9, 1.7 Hz, 2H), 1.66 (s, 3H), 1.61 (s, 3H). 31P NMR (121 MHz, DMSO-d6) δ37.186. 19F NMR (282 MHz, DMSO-d6) δ-105.14. quenched at 0° C. with 30 mL of saturated NH4Cl resulting in the formation of a white precipitate The mixture was concentrated on a rotary evaporator partitioned between EtOAc (200 mL) and H2O (200 mL), upon which the layers were separated The aqueous layer was extracted with EtOAc (3×100 mL) the combined organics washed with brine dried over MgSO4 concentrated The crude product was purified by silica gel flash chromatography (eluted with 5% MeOH/DCM)

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

実験手順: A sealed pressure flask, flushed with N2, containing a mixture of 3.90 g (22.7 mmol) of 1-(Dimethyl-phosphinoyl)-4-fluoro-benzene and 6.0 g (113.3 mmol) of LiNO2 (for prep see, W. C. Ball and H. H. Abram J. Chem. Soc. 1913, 103, 2130-2134) in 27 mL of DMPU (1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone) was stirred at ambient temperature for 5-10 min (to dissolve fluoro compound) then heated at 190° C. for 3 days. The resulting dark brown solution was cooled to ambient temperature, diluted with 300 mL of brine, then extracted with EtOAc (10×100 mL) until the aqueous layer showed little or no evidence of product by HPLC. The combined organics were dried over MgSO4 and concentrated. The excess DMPU was removed via short-path distillation (120° C./0.3 mm) to provide a semi-solid, which was dissolved in a minimum amount of iPrOH and purified by silica gel flash chromatography (eluted with 5% iPrOH/DCM, then 10% iPrOH/DCM, then 15% iPrOH/DCM) to provide 2.04 g of an yellow solid: 1H NMR (300 MHz, DMSO-d6) δ 8.34 (dd, J=8.7, 1.9 Hz, 2H), 8.07 (dd, J=10.6, 8.8 Hz, 2H), 1.75 (s, 3H), 1.70 (s, 3H). 31P NMR (121 MHz, DMSO-d6) δ 37.89. A sealed pressure flask, flushed with N2 containing then heated at 190° C. for 3 days The resulting dark brown solution was cooled to ambient temperature extracted with EtOAc (10×100 mL) until the aqueous layer The combined organics were dried over MgSO4 concentrated The excess DMPU was removed via short-path distillation (120° C./0.3 mm) to provide a semi-solid, which purified by silica gel flash chromatography ( eluted with 5% iPrOH/DCM

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a cooled (0° C.) flask containing 34.0 mL (2.0 M in Et2O, 68.4 mmol) of 4-fluorophenylmagnesium bromide, under an atmosphere of N2, was added a solution of dimethylphosphinic chloride (3.50 g, 31.1 mmol) in 84 mL of THF, dropwise via cannulation, over 20 min. The green reaction mixture was stirred at 0° C. for 1 h, then quenched at 0° C. with 30 mL of saturated NH4Cl resulting in the formation of a white precipitate. The mixture was concentrated on a rotary evaporator and partitioned between EtOAc (200 mL) and H2O (200 mL), upon which the layers were separated. The aqueous layer was extracted with EtOAc (3×100 mL) and the combined organics washed with brine, then dried over MgSO4 and concentrated. The crude product was purified by silica gel flash chromatography (eluted with 5% MeOH/DCM) to provide 2.08 g of an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ 7.83 (m, 2H), 7.35 (td, J=8.9, 1.7 Hz, 2H), 1.66 (s, 3H), 1.61 (s, 3H). 31P NMR (121 MHz, DMSO-d6) δ 37.186. 19F NMR (282 MHz, DMSO-d6) δ-105.14. quenched at 0° C. with 30 mL of saturated NH4Cl resulting in the formation of a white precipitate The mixture was concentrated on a rotary evaporator partitioned between EtOAc (200 mL) and H2O (200 mL), upon which the layers were separated The aqueous layer was extracted with EtOAc (3×100 mL) the combined organics washed with brine dried over MgSO4 concentrated The crude product was purified by silica gel flash chromatography (eluted with 5% MeOH/DCM)

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

実験手順: A sealed pressure flask, flushed with N2, containing a mixture of 3.90 g (22.7 mmol) of 1-(Dimethyl-phosphinoyl)-4-fluoro-benzene and 6.0 g (113.3 mmol) of LiNO2 (for prep see, W. C. Ball and H. H. Abram J. Chem. Soc. 1913, 103, 2130-2134) in 27 mL of DMPU (1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone) was stirred at ambient temperature for 5-10 min (to dissolve fluoro compound) then heated at 190° C. for 3 days. The resulting dark brown solution was cooled to ambient temperature, diluted with 300 mL of brine, then extracted with EtOAc (10×100 mL) until the aqueous layer showed little or no evidence of product by HPLC. The combined organics were dried over MgSO4 and concentrated. The excess DMPU was removed via short-path distillation (120° C./0.3 mm) to provide a semi-solid, which was dissolved in a minimum amount of iPrOH and purified by silica gel flash chromatography (eluted with 5% iPrOH/DCM, then 10% iPrOH/DCM, then 15% iPrOH/DCM) to provide 2.04 g of an yellow solid: 1H NMR (300 MHz, DMSO-d6) δ8.34 (dd, J=8.7, 1.9 Hz, 2H), 8.07 (dd, J=10.6, 8.8 Hz, 2H), 1.75 (s, 3H), 1.70 (s, 3H). 31P NMR (121 MHz, DMSO-d6) δ37.89. A sealed pressure flask, flushed with N2 containing then heated at 190° C. for 3 days The resulting dark brown solution was cooled to ambient temperature extracted with EtOAc (10×100 mL) until the aqueous layer The combined organics were dried over MgSO4 concentrated The excess DMPU was removed via short-path distillation (120° C./0.3 mm) to provide a semi-solid, which purified by silica gel flash chromatography ( eluted with 5% iPrOH/DCM

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a cooled (0° C.) flask containing 34.0 mL (2.0 M in Et2O, 68.4 mmol) of 4-fluorophenylmagnesium bromide, under an atmosphere of N2, was added a solution of dimethylphosphinic chloride (3.50 g, 31.1 mmol) in 84 mL of THF, dropwise via cannulation, over 20 min. The green reaction mixture was stirred at 0° C. for 1 h, then quenched at 0° C. with 30 mL of saturated NH4Cl resulting in the formation of a white precipitate. The mixture was concentrated on a rotary evaporator and partitioned between EtOAc (200 mL) and H2O (200 mL), upon which the layers were separated. The aqueous layer was extracted with EtOAc (3×100 mL) and the combined organics washed with brine, then dried over MgSO4 and concentrated. The crude product was purified by silica gel flash chromatography (eluted with 5% MeOH/DCM) to provide 2.08 g of an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ7.83 (m, 2H), 7.35 (td, J=8.9, 1.7 Hz, 2H), 1.66 (s, 3H), 1.61 (s, 3H). 31P NMR (121 MHz, DMSO-d6) δ37.186. 19F NMR (282 MHz, DMSO-d6) δ-105.14. quenched at 0° C. with 30 mL of saturated NH4Cl resulting in the formation of a white precipitate The mixture was concentrated on a rotary evaporator partitioned between EtOAc (200 mL) and H2O (200 mL), upon which the layers were separated The aqueous layer was extracted with EtOAc (3×100 mL) the combined organics washed with brine dried over MgSO4 concentrated The crude product was purified by silica gel flash chromatography (eluted with 5% MeOH/DCM)

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

実験手順: A sealed pressure flask, flushed with N2, containing a mixture of 3.90 g (22.7 mmol) of 1-(Dimethyl-phosphinoyl)-4-fluoro-benzene and 6.0 g (113.3 mmol) of LiNO2 (for prep see, W. C. Ball and H. H. Abram J. Chem. Soc. 1913, 103, 2130-2134) in 27 mL of DMPU (1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone) was stirred at ambient temperature for 5-10 min (to dissolve fluoro compound) then heated at 190° C. for 3 days. The resulting dark brown solution was cooled to ambient temperature, diluted with 300 mL of brine, then extracted with EtOAc (10×100 mL) until the aqueous layer showed little or no evidence of product by HPLC. The combined organics were dried over MgSO4 and concentrated. The excess DMPU was removed via short-path distillation (120° C./0.3 mm) to provide a semi-solid, which was dissolved in a minimum amount of iPrOH and purified by silica gel flash chromatography (eluted with 5% iPrOH/DCM, then 10% iPrOH/DCM, then 15% iPrOH/DCM) to provide 2.04 g of an yellow solid: 1H NMR (300 MHz, DMSO-d6) δ 8.34 (dd, J=8.7, 1.9 Hz, 2H), 8.07 (dd, J=10.6, 8.8 Hz, 2H), 1.75 (s, 3H), 1.70 (s, 3H). 31P NMR (121 MHz, DMSO-d6) δ 37.89. A sealed pressure flask, flushed with N2 containing then heated at 190° C. for 3 days The resulting dark brown solution was cooled to ambient temperature extracted with EtOAc (10×100 mL) until the aqueous layer The combined organics were dried over MgSO4 concentrated The excess DMPU was removed via short-path distillation (120° C./0.3 mm) to provide a semi-solid, which purified by silica gel flash chromatography ( eluted with 5% iPrOH/DCM