3-phenyloxan-4-one

反応条件: temp:58.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3-phenyldihydro-2H-pyran-4(3H)-one (Intermediate I(2)) (3 g, 17.02 mmol) and carbonisocyanatidic chloride (10.48 g, 29.8 mmol) in a sealed tube was heated to 58° C. and stirred for 1 h. The mixture was then brought to 130° C. and stirred for an additional 2 h. The reaction turned black during this time. After cooling to RT, the tar was taken up in EtOAc (100 mL). The resulting solution was washed with saturated aqueous sodium bicarbonate (2×50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography (Silica, EtOAc/Hexanes) gave 8-phenyl-7,8-dihydropyrano[3,4-e][1,3]oxazine-2,4(3H,5H)-dione (2.58 g, 10.52 mmol, 61.8% yield) as a brown solid. LC-MS (M+H)+=246.0. 1H NMR (500 MHz, MeOD) δ ppm 7.34-7.41 (4H, m), 7.29-7.34 (1H, m), 4.42-4.63 (2H, m), 4.08-4.15 (1H, m), 3.94 (1H, dd, J=11.44, 4.12 Hz), 3.85 (1H, ddd, J=4.20, 2.44, 2.21 Hz). was then brought to 130° C. stirred for an additional 2 h After cooling to RT The resulting solution was washed with saturated aqueous sodium bicarbonate (2×50 mL), brine (50 mL) dried over MgSO4 filtered concentrated in vacuo Purification by flash chromatography (Silica, EtOAc/Hexanes)

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

実験手順: To a stirred mixture of phenylboronic acid (16.81 g, 138 mmol), trans-2-Aminocyclohexanol hydrochloride (1.393 g, 9.19 mmol), and Nickel(II) chloride hexahydrate (1.092 g, 4.59 mmol) in THF (92 mL) at 0° C. was added Sodium bis(trimethylsilyl)amide (1.0 M in THF) (184 mL, 184 mmol) dropwise over 10 min. When the addition was complete, the reaction mixture was sparged with N2 for 15 min. To the reaction mixture at 0° C. was then added 2-Propanol (375 mL) (previously sparged with N2). The resulting mixture was allowed to come to RT at which time 3-iodo-4,4-dimethoxytetrahydro-2H-pyran (Intermediate I(1)) (25 g, 92 mmol) was added dropwise over 5 min. The reaction mixture was then brought to 60° C. and stirred overnight. The reaction mixture was then cooled to 0° C. and quenched by the careful addition of aqu. 1 N HCl until acidic. The resulting mixture was extracted with EtOAc (3×150 mL). The combined organic extracts were washed with Brine (100 mL), dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography (Silica, EtOAc/Hexanes) gave 3-phenyldihydro-2H-pyran-4(3H)-one (8.37 g, 47.5 mmol, 51.7% yield) as a slightly orange oil. 1H NMR (500 MHz, CDCl3) δ ppm 7.32-7.39 (2H, m), 7.26-7.31 (1H, m), 7.21-7.26 (2H, m), 4.17-4.31 (2H, m), 3.91-4.05 (2H, m), 3.78 (1H, dd, J=8.55, 6.10 Hz), 2.61-2.74 (1H, m), 2.51-2.61 (1H, m). When the addition the reaction mixture was sparged with N2 for 15 min at 0° C. added 2-Propanol (375 mL) (previously sparged with N2) was added dropwise over 5 min was then brought to 60° C. quenched by the careful addition of aqu The resulting mixture was extracted with EtOAc (3×150 mL) The combined organic extracts were washed with Brine (100 mL) dried over MgSO4 filtered concentrated in vacuo Purification by flash chromatography (Silica, EtOAc/Hexanes)

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

実験手順: To a stirred mixture of phenylboronic acid (16.81 g, 138 mmol), trans-2-Aminocyclohexanol hydrochloride (1.393 g, 9.19 mmol), and Nickel(II) chloride hexahydrate (1.092 g, 4.59 mmol) in THF (92 mL) at 0° C. was added Sodium bis(trimethylsilyl)amide (1.0 M in THF) (184 mL, 184 mmol) dropwise over 10 min. When the addition was complete, the reaction mixture was sparged with N2 for 15 min. To the reaction mixture at 0° C. was then added 2-Propanol (375 mL) (previously sparged with N2). The resulting mixture was allowed to come to RT at which time 3-iodo-4,4-dimethoxytetrahydro-2H-pyran (Intermediate I(1)) (25 g, 92 mmol) was added dropwise over 5 min. The reaction mixture was then brought to 60° C. and stirred overnight. The reaction mixture was then cooled to 0° C. and quenched by the careful addition of aqu. 1 N HCl until acidic. The resulting mixture was extracted with EtOAc (3×150 mL). The combined organic extracts were washed with Brine (100 mL), dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography (Silica, EtOAc/Hexanes) gave 3-phenyldihydro-2H-pyran-4(3H)-one (8.37 g, 47.5 mmol, 51.7% yield) as a slightly orange oil. 1H NMR (500 MHz, CDCl3) δ ppm 7.32-7.39 (2H, m), 7.26-7.31 (1H, m), 7.21-7.26 (2H, m), 4.17-4.31 (2H, m), 3.91-4.05 (2H, m), 3.78 (1H, dd, J=8.55, 6.10 Hz), 2.61-2.74 (1H, m), 2.51-2.61 (1H, m). When the addition the reaction mixture was sparged with N2 for 15 min at 0° C. added 2-Propanol (375 mL) (previously sparged with N2) was added dropwise over 5 min was then brought to 60° C. quenched by the careful addition of aqu The resulting mixture was extracted with EtOAc (3×150 mL) The combined organic extracts were washed with Brine (100 mL) dried over MgSO4 filtered concentrated in vacuo Purification by flash chromatography (Silica, EtOAc/Hexanes)

反応条件: temp:58.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3-phenyldihydro-2H-pyran-4(3H)-one (Intermediate I(2)) (3 g, 17.02 mmol) and carbonisocyanatidic chloride (10.48 g, 29.8 mmol) in a sealed tube was heated to 58° C. and stirred for 1 h. The mixture was then brought to 130° C. and stirred for an additional 2 h. The reaction turned black during this time. After cooling to RT, the tar was taken up in EtOAc (100 mL). The resulting solution was washed with saturated aqueous sodium bicarbonate (2×50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography (Silica, EtOAc/Hexanes) gave 8-phenyl-7,8-dihydropyrano[3,4-e][1,3]oxazine-2,4(3H,5H)-dione (2.58 g, 10.52 mmol, 61.8% yield) as a brown solid. LC-MS (M+H)+=246.0. 1H NMR (500 MHz, MeOD) δ ppm 7.34-7.41 (4H, m), 7.29-7.34 (1H, m), 4.42-4.63 (2H, m), 4.08-4.15 (1H, m), 3.94 (1H, dd, J=11.44, 4.12 Hz), 3.85 (1H, ddd, J=4.20, 2.44, 2.21 Hz). was then brought to 130° C. stirred for an additional 2 h After cooling to RT The resulting solution was washed with saturated aqueous sodium bicarbonate (2×50 mL), brine (50 mL) dried over MgSO4 filtered concentrated in vacuo Purification by flash chromatography (Silica, EtOAc/Hexanes)

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

実験手順: To a stirred mixture of phenylboronic acid (16.81 g, 138 mmol), trans-2-Aminocyclohexanol hydrochloride (1.393 g, 9.19 mmol), and Nickel(II) chloride hexahydrate (1.092 g, 4.59 mmol) in THF (92 mL) at 0° C. was added Sodium bis(trimethylsilyl)amide (1.0 M in THF) (184 mL, 184 mmol) dropwise over 10 min. When the addition was complete, the reaction mixture was sparged with N2 for 15 min. To the reaction mixture at 0° C. was then added 2-Propanol (375 mL)(previously sparged with N2). The resulting mixture was allowed to come to RT at which time 3-iodo-4,4-dimethoxytetrahydro-2H-pyran (Intermediate I(1)) (25 g, 92 mmol) was added dropwise over 5 min. The reaction mixture was then brought to 60° C. and stirred overnight. The reaction mixture was then cooled to 0° C. and quenched by the careful addition of aqu. 1 N HCl until acidic. The resulting mixture was extracted with EtOAc (3×150 mL). The combined organic extracts were washed with Brine (100 mL), dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography (Silica, EtOAc/Hexanes) gave 3-phenyldihydro-2H-pyran-4(3H)-one (8.37 g, 47.5 mmol, 51.7% yield) as a slightly orange oil. 1H NMR (500 MHz, CDCl3) δ ppm 7.32-7.39 (2H, m), 7.26-7.31 (1H, m), 7.21-7.26 (2H, m), 4.17-4.31 (2H, m), 3.91-4.05 (2H, m), 3.78 (1H, dd, J=8.55, 6.10 Hz), 2.61-2.74 (1H, m), 2.51-2.61 (1H, m). When the addition the reaction mixture was sparged with N2 for 15 min at 0° C. added 2-Propanol (375 mL)(previously sparged with N2) was added dropwise over 5 min was then brought to 60° C. quenched by the careful addition of aqu The resulting mixture was extracted with EtOAc (3×150 mL) The combined organic extracts were washed with Brine (100 mL) dried over MgSO4 filtered concentrated in vacuo Purification by flash chromatography (Silica, EtOAc/Hexanes)

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

実験手順: To a stirred mixture of phenylboronic acid (16.81 g, 138 mmol), trans-2-Aminocyclohexanol hydrochloride (1.393 g, 9.19 mmol), and Nickel(II) chloride hexahydrate (1.092 g, 4.59 mmol) in THF (92 mL) at 0° C. was added Sodium bis(trimethylsilyl)amide (1.0 M in THF) (184 mL, 184 mmol) dropwise over 10 min. When the addition was complete, the reaction mixture was sparged with N2 for 15 min. To the reaction mixture at 0° C. was then added 2-Propanol (375 mL)(previously sparged with N2). The resulting mixture was allowed to come to RT at which time 3-iodo-4,4-dimethoxytetrahydro-2H-pyran (Intermediate I(1)) (25 g, 92 mmol) was added dropwise over 5 min. The reaction mixture was then brought to 60° C. and stirred overnight. The reaction mixture was then cooled to 0° C. and quenched by the careful addition of aqu. 1 N HCl until acidic. The resulting mixture was extracted with EtOAc (3×150 mL). The combined organic extracts were washed with Brine (100 mL), dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography (Silica, EtOAc/Hexanes) gave 3-phenyldihydro-2H-pyran-4(3H)-one (8.37 g, 47.5 mmol, 51.7% yield) as a slightly orange oil. 1H NMR (500 MHz, CDCl3) δ ppm 7.32-7.39 (2H, m), 7.26-7.31 (1H, m), 7.21-7.26 (2H, m), 4.17-4.31 (2H, m), 3.91-4.05 (2H, m), 3.78 (1H, dd, J=8.55, 6.10 Hz), 2.61-2.74 (1H, m), 2.51-2.61 (1H, m). When the addition the reaction mixture was sparged with N2 for 15 min at 0° C. added 2-Propanol (375 mL)(previously sparged with N2) was added dropwise over 5 min was then brought to 60° C. quenched by the careful addition of aqu The resulting mixture was extracted with EtOAc (3×150 mL) The combined organic extracts were washed with Brine (100 mL) dried over MgSO4 filtered concentrated in vacuo Purification by flash chromatography (Silica, EtOAc/Hexanes)

反応条件: temp:58.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3-phenyldihydro-2H-pyran-4(3H)-one (Intermediate I(2)) (3 g, 17.02 mmol) and carbonisocyanatidic chloride (10.48 g, 29.8 mmol) in a sealed tube was heated to 58° C. and stirred for 1 h. The mixture was then brought to 130° C. and stirred for an additional 2 h. The reaction turned black during this time. After cooling to RT, the tar was taken up in EtOAc (100 mL). The resulting solution was washed with saturated aqueous sodium bicarbonate (2×50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography (Silica, EtOAc/Hexanes) gave 8-phenyl-7,8-dihydropyrano[3,4-e][1,3]oxazine-2,4(3H,5H)-dione (2.58 g, 10.52 mmol, 61.8% yield) as a brown solid. LC-MS (M+H)+=246.0. 1H NMR (500 MHz, MeOD) δ ppm 7.34-7.41 (4 H, m), 7.29-7.34 (1 H, m), 4.42-4.63 (2 H, m), 4.08-4.15 (1 H, m), 3.94 (1 H, dd, J=11.44, 4.12 Hz), 3.85 (1 H, ddd, J=4.20, 2.44, 2.21 Hz). was then brought to 130° C. stirred for an additional 2 h After cooling to RT The resulting solution was washed with saturated aqueous sodium bicarbonate (2×50 mL), brine (50 mL) dried over MgSO4 filtered concentrated in vacuo Purification by flash chromatography (Silica, EtOAc/Hexanes)

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

実験手順: To a stirred mixture of phenylboronic acid (16.81 g, 138 mmol), trans-2-Aminocyclohexanol hydrochloride (1.393 g, 9.19 mmol), and Nickel(II) chloride hexahydrate (1.092 g, 4.59 mmol) in THF (92 mL) at 0° C. was added Sodium bis(trimethylsilyl)amide (1.0 M in THF) (184 mL, 184 mmol) dropwise over 10 min. When the addition was complete, the reaction mixture was sparged with N2 for 15 min. To the reaction mixture at 0° C. was then added 2-Propanol (375 mL) (previously sparged with N2). The resulting mixture was allowed to come to RT at which time 3-iodo-4,4-dimethoxytetrahydro-2H-pyran (Intermediate I(1)) (25 g, 92 mmol) was added dropwise over 5 min. The reaction mixture was then brought to 60° C. and stirred overnight. The reaction mixture was then cooled to 0° C. and quenched by the careful addition of aqu. 1 N HCl until acidic. The resulting mixture was extracted with EtOAc (3×150 mL). The combined organic extracts were washed with Brine (100 mL), dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography (Silica, EtOAc/Hexanes) gave 3-phenyldihydro-2H-pyran-4(3H)-one (8.37 g, 47.5 mmol, 51.7% yield) as a slightly orange oil. 1H NMR (500 MHz, CDCl3) δ ppm 7.32-7.39 (2 H, m), 7.26-7.31 (1 H, m), 7.21-7.26 (2 H, m), 4.17-4.31 (2 H, m), 3.91-4.05 (2 H, m), 3.78 (1 H, dd, J=8.55, 6.10 Hz), 2.61-2.74 (1 H, m), 2.51-2.61 (1 H, m). When the addition the reaction mixture was sparged with N2 for 15 min at 0° C. added 2-Propanol (375 mL) (previously sparged with N2) was added dropwise over 5 min was then brought to 60° C. quenched by the careful addition of aqu The resulting mixture was extracted with EtOAc (3×150 mL) The combined organic extracts were washed with Brine (100 mL) dried over MgSO4 filtered concentrated in vacuo Purification by flash chromatography (Silica, EtOAc/Hexanes)

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

実験手順: To a stirred mixture of phenylboronic acid (16.81 g, 138 mmol), trans-2-Aminocyclohexanol hydrochloride (1.393 g, 9.19 mmol), and Nickel(II) chloride hexahydrate (1.092 g, 4.59 mmol) in THF (92 mL) at 0° C. was added Sodium bis(trimethylsilyl)amide (1.0 M in THF) (184 mL, 184 mmol) dropwise over 10 min. When the addition was complete, the reaction mixture was sparged with N2 for 15 min. To the reaction mixture at 0° C. was then added 2-Propanol (375 mL) (previously sparged with N2). The resulting mixture was allowed to come to RT at which time 3-iodo-4,4-dimethoxytetrahydro-2H-pyran (Intermediate I(1)) (25 g, 92 mmol) was added dropwise over 5 min. The reaction mixture was then brought to 60° C. and stirred overnight. The reaction mixture was then cooled to 0° C. and quenched by the careful addition of aqu. 1 N HCl until acidic. The resulting mixture was extracted with EtOAc (3×150 mL). The combined organic extracts were washed with Brine (100 mL), dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography (Silica, EtOAc/Hexanes) gave 3-phenyldihydro-2H-pyran-4(3H)-one (8.37 g, 47.5 mmol, 51.7% yield) as a slightly orange oil. 1H NMR (500 MHz, CDCl3) δ ppm 7.32-7.39 (2 H, m), 7.26-7.31 (1 H, m), 7.21-7.26 (2 H, m), 4.17-4.31 (2 H, m), 3.91-4.05 (2 H, m), 3.78 (1 H, dd, J=8.55, 6.10 Hz), 2.61-2.74 (1 H, m), 2.51-2.61 (1 H, m). When the addition the reaction mixture was sparged with N2 for 15 min at 0° C. added 2-Propanol (375 mL) (previously sparged with N2) was added dropwise over 5 min was then brought to 60° C. quenched by the careful addition of aqu The resulting mixture was extracted with EtOAc (3×150 mL) The combined organic extracts were washed with Brine (100 mL) dried over MgSO4 filtered concentrated in vacuo Purification by flash chromatography (Silica, EtOAc/Hexanes)

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

実験手順: To a stirred mixture of phenylboronic acid (16.81 g, 138 mmol), trans-2-Aminocyclohexanol hydrochloride (1.393 g, 9.19 mmol), and Nickel(II) chloride hexahydrate (1.092 g, 4.59 mmol) in THF (92 mL) at 0° C. was added Sodium bis(trimethylsilyl)amide (1.0 M in THF) (184 mL, 184 mmol) dropwise over 10 min. When the addition was complete, the reaction mixture was sparged with N2 for 15 min. To the reaction mixture at 0° C. was then added 2-Propanol (375 mL) (previously sparged with N2). The resulting mixture was allowed to come to RT at which time 3-iodo-4,4-dimethoxytetrahydro-2H-pyran (Intermediate I(1)) (25 g, 92 mmol) was added dropwise over 5 min. The reaction mixture was then brought to 60° C. and stirred overnight. The reaction mixture was then cooled to 0° C. and quenched by the careful addition of aqu. 1 N HCl until acidic. The resulting mixture was extracted with EtOAc (3×150 mL). The combined organic extracts were washed with Brine (100 mL), dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography (Silica, EtOAc/Hexanes) gave 3-phenyldihydro-2H-pyran-4(3H)-one (8.37 g, 47.5 mmol, 51.7% yield) as a slightly orange oil. 1H NMR (500 MHz, CDCl3) δ ppm 7.32-7.39 (2 H, m), 7.26-7.31 (1 H, m), 7.21-7.26 (2 H, m), 4.17-4.31 (2 H, m), 3.91-4.05 (2 H, m), 3.78 (1 H, dd, J=8.55, 6.10 Hz), 2.61-2.74 (1 H, m), 2.51-2.61 (1 H, m). When the addition the reaction mixture was sparged with N2 for 15 min at 0° C. added 2-Propanol (375 mL) (previously sparged with N2) was added dropwise over 5 min was then brought to 60° C. quenched by the careful addition of aqu The resulting mixture was extracted with EtOAc (3×150 mL) The combined organic extracts were washed with Brine (100 mL) dried over MgSO4 filtered concentrated in vacuo Purification by flash chromatography (Silica, EtOAc/Hexanes)

反応条件: temp:58.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3-phenyldihydro-2H-pyran-4(3H)-one (Intermediate I(2)) (3 g, 17.02 mmol) and carbonisocyanatidic chloride (10.48 g, 29.8 mmol) in a sealed tube was heated to 58° C. and stirred for 1 h. The mixture was then brought to 130° C. and stirred for an additional 2 h. The reaction turned black during this time. After cooling to RT, the tar was taken up in EtOAc (100 mL). The resulting solution was washed with saturated aqueous sodium bicarbonate (2×50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography (Silica, EtOAc/Hexanes) gave 8-phenyl-7,8-dihydropyrano[3,4-e][1,3]oxazine-2,4(3H,5H)-dione (2.58 g, 10.52 mmol, 61.8% yield) as a brown solid. LC-MS (M+H)+=246.0. 1H NMR (500 MHz, MeOD) δ ppm 7.34-7.41 (4H, m), 7.29-7.34 (1H, m), 4.42-4.63 (2H, m), 4.08-4.15 (1H, m), 3.94 (1H, dd, J=11.44, 4.12 Hz), 3.85 (1H, ddd, J=4.20, 2.44, 2.21 Hz). was then brought to 130° C. stirred for an additional 2 h After cooling to RT The resulting solution was washed with saturated aqueous sodium bicarbonate (2×50 mL), brine (50 mL) dried over MgSO4 filtered concentrated in vacuo Purification by flash chromatography (Silica, EtOAc/Hexanes)

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

実験手順: To a stirred mixture of phenylboronic acid (16.81 g, 138 mmol), trans-2-Aminocyclohexanol hydrochloride (1.393 g, 9.19 mmol), and Nickel(II) chloride hexahydrate (1.092 g, 4.59 mmol) in THF (92 mL) at 0° C. was added Sodium bis(trimethylsilyl)amide (1.0 M in THF) (184 mL, 184 mmol) dropwise over 10 min. When the addition was complete, the reaction mixture was sparged with N2 for 15 min. To the reaction mixture at 0° C. was then added 2-Propanol (375 mL) (previously sparged with N2). The resulting mixture was allowed to come to RT at which time 3-iodo-4,4-dimethoxytetrahydro-2H-pyran (Intermediate I(1)) (25 g, 92 mmol) was added dropwise over 5 min. The reaction mixture was then brought to 60° C. and stirred overnight. The reaction mixture was then cooled to 0° C. and quenched by the careful addition of aqu. 1 N HCl until acidic. The resulting mixture was extracted with EtOAc (3×150 mL). The combined organic extracts were washed with Brine (100 mL), dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography (Silica, EtOAc/Hexanes) gave 3-phenyldihydro-2H-pyran-4(3H)-one (8.37 g, 47.5 mmol, 51.7% yield) as a slightly orange oil. 1H NMR (500 MHz, CDCl3) δ ppm 7.32-7.39 (2H, m), 7.26-7.31 (1H, m), 7.21-7.26 (2H, m), 4.17-4.31 (2H, m), 3.91-4.05 (2H, m), 3.78 (1H, dd, J=8.55, 6.10 Hz), 2.61-2.74 (1H, m), 2.51-2.61 (1H, m). When the addition the reaction mixture was sparged with N2 for 15 min at 0° C. added 2-Propanol (375 mL) (previously sparged with N2) was added dropwise over 5 min was then brought to 60° C. quenched by the careful addition of aqu The resulting mixture was extracted with EtOAc (3×150 mL) The combined organic extracts were washed with Brine (100 mL) dried over MgSO4 filtered concentrated in vacuo Purification by flash chromatography (Silica, EtOAc/Hexanes)