4-phenylmorpholin-3-one

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A dry 100 mL Schlenk-type flask was fitted with a nitrogen/vacuum line and charged with 2-bromo-1,3,5-tri-tert-butylbenzene (0.521 g, 1.601 mmol), 20 mL dry THF, and a stirbar. The solution was cooled to −78° C. and treated with 2.5M butyllithium (0.582 ml, 1.456 mmol). The reaction was stirred for 15 min and treated with 4-phenylmorpholin-3-one (0.258 g, 1.456 mmol) dissolved in 2 mL dry THF dropwise over 5 min. The reaction was stirred for 2 h at −78° C. The side arm compartment of the Schlenk-type flask was charged with ˜1 g dry ice. The system was sealed, and the dry ice was allowed to sublime into the solution. After 30 min, a nitrogen needle was fitted to the flask, and a solid was noted in the solution. The cooling bath was removed, which caused the solids to bubble (presumably dry ice). The solution was allowed to warm to RT overnight. The solution was diluted with 40 mL water and extracted with dichloromethane (2×10 mL). The water was concentrated in vacuo and dried at 60° C. and 0.15 mmHg to afford lithium 3-oxo-4-phenylmorpholine-2-carboxylate (0.200 g, 60.5% yield). 1H NMR (400 MHz, D2O) 3.72 (t, J=5.23 Hz, 2 H), 3.99 (dt, J=12.10, 5.29 Hz, 1 H), 4.08 (dt, J=12.15, 5.22 Hz, 1 H), 4.61 (s, 1 H), 7.24-7.28 (m, 2 H), 7.32 (tt, 1 H), 7.38-7.44 (m, 2 H). A dry 100 mL Schlenk-type flask was fitted with a nitrogen/vacuum line The reaction was stirred for 2 h at −78° C The system was sealed After 30 min a nitrogen needle was fitted to the flask The cooling bath was removed to bubble (presumably dry ice) to warm to RT overnight The solution was diluted with 40 mL water extracted with dichloromethane (2×10 mL) The water was concentrated in vacuo dried at 60° C.

Conditions: temp:41.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250-mL flask was charged with 2-anilinoethanol (9.17 ml, 73.2 mmol), 9 mL dry EtOH, an overhead stirrer, a calibrated pH probe, and 27 mL water. An addition funnel was charged with 10 N sodium hydroxide solution (45.4 ml, 454 mmol). The solution was heated to 41° C., and treated with chloracetyl chloride (17.5 ml, 220 mmol) via a syringe pump over 1 h. The sodium hydroxide solution was simultaneously added to the stirring solution so that the pH was maintained between 12 and 12.5. After the addition was complete, the solution was cooled to 0° C. and stirred for 1 h. The solids were collected and washed with water (2×60 mL cold water). The solids were dried at 50° C. at 0.2 mm Hg for 36 h to afford 4-phenylmorpholin-3-one (8.10 g, 62.5% yield). 1H NMR (400 MHz, CHLOROFORM-d) 3.75-3.80 (m, 2 H) 4.02-4.06 (m, 2 H) 4.35 (s, 2 H) 7.27-7.36 (m, 3 H) 7.39-7.46 (m, 2 H). 13C NMR (101 MHz, CHLOROFORM-d) 49.69 (s, 1 C) 64.14 (s, 1 C) 68.57 (s, 1 C) 125.48 (s, 2 C) 127.15 (s, 1 C) 129.30 (s, 2 C) 141.31 (s, 1 C) 166.59 (s, 1 C). was maintained between 12 and 12.5 After the addition the solution was cooled to 0° C. The solids were collected washed with water (2×60 mL cold water) The solids were dried at 50° C. at 0.2 mm Hg for 36 h

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A dry 100 mL Schlenk-type flask was fitted with a nitrogen/vacuum line and charged with 2-bromo-1,3,5-tri-tert-butylbenzene (0.521 g, 1.601 mmol), 20 mL dry THF, and a stirbar. The solution was cooled to −78° C. and treated with 2.5M butyllithium (0.582 ml, 1.456 mmol). The reaction was stirred for 15 min and treated with 4-phenylmorpholin-3-one (0.258 g, 1.456 mmol) dissolved in 2 mL dry THF dropwise over 5 min. The reaction was stirred for 2 h at −78° C. The side arm compartment of the Schlenk-type flask was charged with ˜1 g dry ice. The system was sealed, and the dry ice was allowed to sublime into the solution. After 30 min, a nitrogen needle was fitted to the flask, and a solid was noted in the solution. The cooling bath was removed, which caused the solids to bubble (presumably dry ice). The solution was allowed to warm to RT overnight. The solution was diluted with 40 mL water and extracted with dichloromethane (2×10 mL). The water was concentrated in vacuo and dried at 60° C. and 0.15 mmHg to afford lithium 3-oxo-4-phenylmorpholine-2-carboxylate (0.200 g, 60.5% yield). 1H NMR (400 MHz, D2O) 3.72 (t, J=5.23 Hz, 2 H), 3.99 (dt, J=12.10, 5.29 Hz, 1 H), 4.08 (dt, J=12.15, 5.22 Hz, 1 H), 4.61 (s, 1 H), 7.24-7.28 (m, 2 H), 7.32 (tt, 1 H), 7.38-7.44 (m, 2 H). A dry 100 mL Schlenk-type flask was fitted with a nitrogen/vacuum line The reaction was stirred for 2 h at −78° C The system was sealed After 30 min a nitrogen needle was fitted to the flask The cooling bath was removed to bubble (presumably dry ice) to warm to RT overnight The solution was diluted with 40 mL water extracted with dichloromethane (2×10 mL) The water was concentrated in vacuo dried at 60° C.

Conditions: temp:41.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250-mL flask was charged with 2-anilinoethanol (9.17 ml, 73.2 mmol), 9 mL dry EtOH, an overhead stirrer, a calibrated pH probe, and 27 mL water. An addition funnel was charged with 10 N sodium hydroxide solution (45.4 ml, 454 mmol). The solution was heated to 41° C., and treated with chloracetyl chloride (17.5 ml, 220 mmol) via a syringe pump over 1 h. The sodium hydroxide solution was simultaneously added to the stirring solution so that the pH was maintained between 12 and 12.5. After the addition was complete, the solution was cooled to 0° C. and stirred for 1 h. The solids were collected and washed with water (2×60 mL cold water). The solids were dried at 50° C. at 0.2 mm Hg for 36 h to afford 4-phenylmorpholin-3-one (8.10 g, 62.5% yield). 1H NMR (400 MHz, CHLOROFORM-d) 3.75-3.80 (m, 2 H) 4.02-4.06 (m, 2 H) 4.35 (s, 2 H) 7.27-7.36 (m, 3 H) 7.39-7.46 (m, 2 H). 13C NMR (101 MHz, CHLOROFORM-d) 49.69 (s, 1 C) 64.14 (s, 1 C) 68.57 (s, 1 C) 125.48 (s, 2 C) 127.15 (s, 1 C) 129.30 (s, 2 C) 141.31 (s, 1 C) 166.59 (s, 1 C). was maintained between 12 and 12.5 After the addition the solution was cooled to 0° C. The solids were collected washed with water (2×60 mL cold water) The solids were dried at 50° C. at 0.2 mm Hg for 36 h

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A dry 100 mL Schlenk-type flask was fitted with a nitrogen/vacuum line and charged with 2-bromo-1,3,5-tri-tert-butylbenzene (0.521 g, 1.601 mmol), 20 mL dry THF, and a stirbar. The solution was cooled to −78° C. and treated with 2.5M butyllithium (0.582 ml, 1.456 mmol). The reaction was stirred for 15 min and treated with 4-phenylmorpholin-3-one (0.258 g, 1.456 mmol) dissolved in 2 mL dry THF dropwise over 5 min. The reaction was stirred for 2 h at −78° C. The side arm compartment of the Schlenk-type flask was charged with ˜1 g dry ice. The system was sealed, and the dry ice was allowed to sublime into the solution. After 30 min, a nitrogen needle was fitted to the flask, and a solid was noted in the solution. The cooling bath was removed, which caused the solids to bubble (presumably dry ice). The solution was allowed to warm to RT overnight. The solution was diluted with 40 mL water and extracted with dichloromethane (2×10 mL). The water was concentrated in vacuo and dried at 60° C. and 0.15 mmHg to afford lithium 3-oxo-4-phenylmorpholine-2-carboxylate (0.200 g, 60.5% yield). 1H NMR (400 MHz, D2O) 3.72 (t, J=5.23 Hz, 2 H), 3.99 (dt, J=12.10, 5.29 Hz, 1 H), 4.08 (dt, J=12.15, 5.22 Hz, 1 H), 4.61 (s, 1 H), 7.24-7.28 (m, 2 H), 7.32 (tt, 1 H), 7.38-7.44 (m, 2 H). A dry 100 mL Schlenk-type flask was fitted with a nitrogen/vacuum line The reaction was stirred for 2 h at −78° C The system was sealed After 30 min a nitrogen needle was fitted to the flask The cooling bath was removed to bubble (presumably dry ice) to warm to RT overnight The solution was diluted with 40 mL water extracted with dichloromethane (2×10 mL) The water was concentrated in vacuo dried at 60° C.

Conditions: temp:41.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250-mL flask was charged with 2-anilinoethanol (9.17 ml, 73.2 mmol), 9 mL dry EtOH, an overhead stirrer, a calibrated pH probe, and 27 mL water. An addition funnel was charged with 10 N sodium hydroxide solution (45.4 ml, 454 mmol). The solution was heated to 41° C., and treated with chloracetyl chloride (17.5 ml, 220 mmol) via a syringe pump over 1 h. The sodium hydroxide solution was simultaneously added to the stirring solution so that the pH was maintained between 12 and 12.5. After the addition was complete, the solution was cooled to 0° C. and stirred for 1 h. The solids were collected and washed with water (2×60 mL cold water). The solids were dried at 50° C. at 0.2 mm Hg for 36 h to afford 4-phenylmorpholin-3-one (8.10 g, 62.5% yield). 1H NMR (400 MHz, CHLOROFORM-d) 3.75-3.80 (m, 2 H) 4.02-4.06 (m, 2 H) 4.35 (s, 2 H) 7.27-7.36 (m, 3 H) 7.39-7.46 (m, 2 H). 13C NMR (101 MHz, CHLOROFORM-d) 49.69 (s, 1 C) 64.14 (s, 1 C) 68.57 (s, 1 C) 125.48 (s, 2 C) 127.15 (s, 1 C) 129.30 (s, 2 C) 141.31 (s, 1 C) 166.59 (s, 1 C). was maintained between 12 and 12.5 After the addition the solution was cooled to 0° C. The solids were collected washed with water (2×60 mL cold water) The solids were dried at 50° C. at 0.2 mm Hg for 36 h

Conditions: temp:41.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250-mL flask was charged with 2-anilinoethanol (9.17 ml, 73.2 mmol), 9 mL dry EtOH, an overhead stirrer, a calibrated pH probe, and 27 mL water. An addition funnel was charged with 10 N sodium hydroxide solution (45.4 ml, 454 mmol). The solution was heated to 41° C., and treated with chloracetyl chloride (17.5 ml, 220 mmol) via a syringe pump over 1 h. The sodium hydroxide solution was simultaneously added to the stirring solution so that the pH was maintained between 12 and 12.5. After the addition was complete, the solution was cooled to 0° C. and stirred for 1 h. The solids were collected and washed with water (2×60 mL cold water). The solids were dried at 50° C. at 0.2 mm Hg for 36 h to afford 4-phenylmorpholin-3-one (8.10 g, 62.5% yield). 1H NMR (400 MHz, CHLOROFORM-d) 3.75-3.80 (m, 2 H) 4.02-4.06 (m, 2 H) 4.35 (s, 2 H) 7.27-7.36 (m, 3 H) 7.39-7.46 (m, 2 H). 13C NMR (101 MHz, CHLOROFORM-d) 49.69 (s, 1 C) 64.14 (s, 1 C) 68.57 (s, 1 C) 125.48 (s, 2 C) 127.15 (s, 1 C) 129.30 (s, 2 C) 141.31 (s, 1 C) 166.59 (s, 1 C). was maintained between 12 and 12.5 After the addition the solution was cooled to 0° C. The solids were collected washed with water (2×60 mL cold water) The solids were dried at 50° C. at 0.2 mm Hg for 36 h

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A dry 100 mL Schlenk-type flask was fitted with a nitrogen/vacuum line and charged with 2-bromo-1,3,5-tri-tert-butylbenzene (0.521 g, 1.601 mmol), 20 mL dry THF, and a stirbar. The solution was cooled to −78° C. and treated with 2.5M butyllithium (0.582 ml, 1.456 mmol). The reaction was stirred for 15 min and treated with 4-phenylmorpholin-3-one (0.258 g, 1.456 mmol) dissolved in 2 mL dry THF dropwise over 5 min. The reaction was stirred for 2 h at −78° C. The side arm compartment of the Schlenk-type flask was charged with ˜1 g dry ice. The system was sealed, and the dry ice was allowed to sublime into the solution. After 30 min, a nitrogen needle was fitted to the flask, and a solid was noted in the solution. The cooling bath was removed, which caused the solids to bubble (presumably dry ice). The solution was allowed to warm to RT overnight. The solution was diluted with 40 mL water and extracted with dichloromethane (2×10 mL). The water was concentrated in vacuo and dried at 60° C. and 0.15 mmHg to afford lithium 3-oxo-4-phenylmorpholine-2-carboxylate (0.200 g, 60.5% yield). 1H NMR (400 MHz, D2O) 3.72 (t, J=5.23 Hz, 2 H), 3.99 (dt, J=12.10, 5.29 Hz, 1 H), 4.08 (dt, J=12.15, 5.22 Hz, 1 H), 4.61 (s, 1 H), 7.24-7.28 (m, 2 H), 7.32 (tt, 1 H), 7.38-7.44 (m, 2 H). A dry 100 mL Schlenk-type flask was fitted with a nitrogen/vacuum line The reaction was stirred for 2 h at −78° C The system was sealed After 30 min a nitrogen needle was fitted to the flask The cooling bath was removed to bubble (presumably dry ice) to warm to RT overnight The solution was diluted with 40 mL water extracted with dichloromethane (2×10 mL) The water was concentrated in vacuo dried at 60° C.

Conditions: temp:41.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250-mL flask was charged with 2-anilinoethanol (9.17 ml, 73.2 mmol), 9 mL dry EtOH, an overhead stirrer, a calibrated pH probe, and 27 mL water. An addition funnel was charged with 10 N sodium hydroxide solution (45.4 ml, 454 mmol). The solution was heated to 41° C., and treated with chloracetyl chloride (17.5 ml, 220 mmol) via a syringe pump over 1 h. The sodium hydroxide solution was simultaneously added to the stirring solution so that the pH was maintained between 12 and 12.5. After the addition was complete, the solution was cooled to 0° C. and stirred for 1 h. The solids were collected and washed with water (2×60 mL cold water). The solids were dried at 50° C. at 0.2 mm Hg for 36 h to afford 4-phenylmorpholin-3-one (8.10 g, 62.5% yield). 1H NMR (400 MHz, CHLOROFORM-d) 3.75-3.80 (m, 2 H) 4.02-4.06 (m, 2 H) 4.35 (s, 2 H) 7.27-7.36 (m, 3 H) 7.39-7.46 (m, 2 H). 13C NMR (101 MHz, CHLOROFORM-d) 49.69 (s, 1 C) 64.14 (s, 1 C) 68.57 (s, 1 C) 125.48 (s, 2 C) 127.15 (s, 1 C) 129.30 (s, 2 C) 141.31 (s, 1 C) 166.59 (s, 1 C). was maintained between 12 and 12.5 After the addition the solution was cooled to 0° C. The solids were collected washed with water (2×60 mL cold water) The solids were dried at 50° C. at 0.2 mm Hg for 36 h

Conditions: temp:41.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250-mL flask was charged with 2-anilinoethanol (9.17 ml, 73.2 mmol), 9 mL dry EtOH, an overhead stirrer, a calibrated pH probe, and 27 mL water. An addition funnel was charged with 10 N sodium hydroxide solution (45.4 ml, 454 mmol). The solution was heated to 41° C., and treated with chloracetyl chloride (17.5 ml, 220 mmol) via a syringe pump over 1 h. The sodium hydroxide solution was simultaneously added to the stirring solution so that the pH was maintained between 12 and 12.5. After the addition was complete, the solution was cooled to 0° C. and stirred for 1 h. The solids were collected and washed with water (2×60 mL cold water). The solids were dried at 50° C. at 0.2 mm Hg for 36 h to afford 4-phenylmorpholin-3-one (8.10 g, 62.5% yield). 1H NMR (400 MHz, CHLOROFORM-d) 3.75-3.80 (m, 2 H) 4.02-4.06 (m, 2 H) 4.35 (s, 2 H) 7.27-7.36 (m, 3 H) 7.39-7.46 (m, 2 H). 13C NMR (101 MHz, CHLOROFORM-d) 49.69 (s, 1 C) 64.14 (s, 1 C) 68.57 (s, 1 C) 125.48 (s, 2 C) 127.15 (s, 1 C) 129.30 (s, 2 C) 141.31 (s, 1 C) 166.59 (s, 1 C). was maintained between 12 and 12.5 After the addition the solution was cooled to 0° C. The solids were collected washed with water (2×60 mL cold water) The solids were dried at 50° C. at 0.2 mm Hg for 36 h

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A dry 100 mL Schlenk-type flask was fitted with a nitrogen/vacuum line and charged with 2-bromo-1,3,5-tri-tert-butylbenzene (0.521 g, 1.601 mmol), 20 mL dry THF, and a stirbar. The solution was cooled to −78° C. and treated with 2.5M butyllithium (0.582 ml, 1.456 mmol). The reaction was stirred for 15 min and treated with 4-phenylmorpholin-3-one (0.258 g, 1.456 mmol) dissolved in 2 mL dry THF dropwise over 5 min. The reaction was stirred for 2 h at −78° C. The side arm compartment of the Schlenk-type flask was charged with ˜1 g dry ice. The system was sealed, and the dry ice was allowed to sublime into the solution. After 30 min, a nitrogen needle was fitted to the flask, and a solid was noted in the solution. The cooling bath was removed, which caused the solids to bubble (presumably dry ice). The solution was allowed to warm to RT overnight. The solution was diluted with 40 mL water and extracted with dichloromethane (2×10 mL). The water was concentrated in vacuo and dried at 60° C. and 0.15 mmHg to afford lithium 3-oxo-4-phenylmorpholine-2-carboxylate (0.200 g, 60.5% yield). 1H NMR (400 MHz, D2O) 3.72 (t, J=5.23 Hz, 2H), 3.99 (dt, J=12.10, 5.29 Hz, 1H), 4.08 (dt, J=12.15, 5.22 Hz, 1H), 4.61 (s, 1H), 7.24-7.28 (m, 2H), 7.32 (tt, 1H), 7.38-7.44 (m, 2H). A dry 100 mL Schlenk-type flask was fitted with a nitrogen/vacuum line The reaction was stirred for 2 h at −78° C The system was sealed After 30 min a nitrogen needle was fitted to the flask The cooling bath was removed to bubble (presumably dry ice) to warm to RT overnight The solution was diluted with 40 mL water extracted with dichloromethane (2×10 mL) The water was concentrated in vacuo dried at 60° C.

Conditions: temp:41.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250-mL flask was charged with 2-anilinoethanol (9.17 ml, 73.2 mmol), 9 mL dry EtOH, an overhead stirrer, a calibrated pH probe, and 27 mL water. An addition funnel was charged with 10 N sodium hydroxide solution (45.4 ml, 454 mmol). The solution was heated to 41° C., and treated with chloracetyl chloride (17.5 ml, 220 mmol) via a syringe pump over 1 h. The sodium hydroxide solution was simultaneously added to the stirring solution so that the pH was maintained between 12 and 12.5. After the addition was complete, the solution was cooled to 0° C. and stirred for 1 h. The solids were collected and washed with water (2×60 mL cold water). The solids were dried at 50° C. at 0.2 mm Hg for 36 h to afford 4-phenylmorpholin-3-one (8.10 g, 62.5% yield). 1H NMR (400 MHz, CHLOROFORM-d) 3.75-3.80 (m, 2H) 4.02-4.06 (m, 2H) 4.35 (s, 2H) 7.27-7.36 (m, 3H) 7.39-7.46 (m, 2H). 13C NMR (101 MHz, CHLOROFORM-d) 49.69 (s, 1 C) 64.14 (s, 1 C) 68.57 (s, 1 C) 125.48 (s, 2 C) 127.15 (s, 1 C) 129.30 (s, 2 C) 141.31 (s, 1 C) 166.59 (s, 1 C). was maintained between 12 and 12.5 After the addition the solution was cooled to 0° C. The solids were collected washed with water (2×60 mL cold water) The solids were dried at 50° C. at 0.2 mm Hg for 36 h