4-(2-fluorophenyl)-5,5-dimethyl-1,3-oxazolidin-2-one

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a nitrogen purged solution of 4-iodo-N-(quinolin-8-yl)benzamide (250 mg, 0.66 mmol) in 1,4-dioxane (5 mL) were added cesium carbonate (435.37 mg, 1.33 mmol), xantphos (77.31 mg, 0.13 mmol), Pd2(dba)3 (61.18 mg, 0.06 mmol) and 4-(2-fluorophenyl)-5,5-dimethyloxazolidin-2-one (167.73 mg, 0.80 mmol). The mixture was purged with nitrogen for 5-10 minutes. The reaction mixture was then stirred for 3 hours at 100° C. After completion of the reaction (monitored by TLC, TLC system: 30% EtOAc in hexane), the reaction mixture was cooled to ambient temperature and filtered through Celite® brand filter aid. The filtrate was concentrated and purified by column chromatography using silica gel and eluting with 30% EtOAc in hexane to afford (R+S) 4-(4-(2-fluorophenyl)-5,5-dimethyl-2-oxooxazolidin-3-yl)-N-(quinolin-8-yl)benzamide (60 mg, 19.71%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.57 (s, 1H), 8.95 (dd, J=1.2 Hz, 1H), 8.68 (d, J=7.6 Hz, 1H), 8.46 (d, J=8.3 Hz, 1H), 8.00-7.95 (m, 2H), 7.82-7.62 (m, 5H), 7.41-7.35 (m, 2H), 7.19-7.08 (m, 2H), 5.84 (s, 1H), 1.69 (s, 3H), 1.03 (s, 3H). m/z (ESI) 456.1 (M+H)+. The mixture was purged with nitrogen for 5-10 minutes After completion of the reaction (monitored by TLC, TLC system: 30% EtOAc in hexane) the reaction mixture was cooled to ambient temperature filtered through Celite® brand filter aid The filtrate was concentrated purified by column chromatography eluting with 30% EtOAc in hexane

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a nitrogen purged solution of 4-iodo-N-(quinolin-8-yl)benzamide (250 mg, 0.66 mmol) in 1,4-dioxane (5 mL) were added cesium carbonate (435.37 mg, 1.33 mmol), xantphos (77.31 mg, 0.13 mmol), Pd2(dba)3 (61.18 mg, 0.06 mmol) and 4-(2-fluorophenyl)-5,5-dimethyloxazolidin-2-one (167.73 mg, 0.80 mmol). The mixture was purged with nitrogen for 5-10 minutes. The reaction mixture was then stirred for 3 hours at 100° C. After completion of the reaction (monitored by TLC, TLC system: 30% EtOAc in hexane), the reaction mixture was cooled to ambient temperature and filtered through Celite® brand filter aid. The filtrate was concentrated and purified by column chromatography using silica gel and eluting with 30% EtOAc in hexane to afford (R+S) 4-(4-(2-fluorophenyl)-5,5-dimethyl-2-oxooxazolidin-3-yl)-N-(quinolin-8-yl)benzamide (60 mg, 19.71%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.57 (s, 1H), 8.95 (dd, J=1.2 Hz, 1H), 8.68 (d, J=7.6 Hz, 1H), 8.46 (d, J=8.3 Hz, 1H), 8.00-7.95 (m, 2H), 7.82-7.62 (m, 5H), 7.41-7.35 (m, 2H), 7.19-7.08 (m, 2H), 5.84 (s, 1H), 1.69 (s, 3H), 1.03 (s, 3H). m/z (ESI) 456.1 (M+H)+. The mixture was purged with nitrogen for 5-10 minutes After completion of the reaction (monitored by TLC, TLC system: 30% EtOAc in hexane) the reaction mixture was cooled to ambient temperature filtered through Celite® brand filter aid The filtrate was concentrated purified by column chromatography eluting with 30% EtOAc in hexane

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

Procedure: To a solution of tert-butyl (1-(2-fluorophenyl)-2-hydroxy-2-methylpropyl)carbamate (400 mg, 1.41 mmol) in THF (8 mL) was added potassium tert-butoxide (316.87 mg, 2.82 mmol) at 0-5° C. The resulting reaction mixture was stirred for 2 hours at ambient temperature. After completion of the reaction (monitored by TLC, TLC system: 50% EtOAc in hexane), the reaction mixture was quenched with ice water and extracted with EtOAc. The combined organic layers were washed with, water, saturated NaCl solution and dried on Na2SO4, filtered, and concentrated under reduced pressure to afford 4-(2-fluorophenyl)-5,5-dimethyloxazolidin-2-one (290 mg, 98.18%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.05 (s, 1H), 7.44-7.35 (m, 2H), 7.30-7.22 (m, 2H), 4.88 (s, 1H), 1.53 (s, 3H), 0.88 (s, 3H). m/z (ESI) 210.1 (M+H)+. The resulting reaction mixture the reaction mixture was quenched with ice water extracted with EtOAc The combined organic layers were washed with, water, saturated NaCl solution dried on Na2SO4 filtered concentrated under reduced pressure

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a nitrogen purged solution of 4-iodo-N-(quinolin-8-yl)benzamide (250 mg, 0.66 mmol) in 1,4-dioxane (5 mL) were added cesium carbonate (435.37 mg, 1.33 mmol), xantphos (77.31 mg, 0.13 mmol), Pd2(dba)3 (61.18 mg, 0.06 mmol) and 4-(2-fluorophenyl)-5,5-dimethyloxazolidin-2-one (167.73 mg, 0.80 mmol). The mixture was purged with nitrogen for 5-10 minutes. The reaction mixture was then stirred for 3 hours at 100° C. After completion of the reaction (monitored by TLC, TLC system: 30% EtOAc in hexane), the reaction mixture was cooled to ambient temperature and filtered through Celite® brand filter aid. The filtrate was concentrated and purified by column chromatography using silica gel and eluting with 30% EtOAc in hexane to afford (R+S) 4-(4-(2-fluorophenyl)-5,5-dimethyl-2-oxooxazolidin-3-yl)-N-(quinolin-8-yl)benzamide (60 mg, 19.71%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.57 (s, 1H), 8.95 (dd, J=1.2 Hz, 1H), 8.68 (d, J=7.6 Hz, 1H), 8.46 (d, J=8.3 Hz, 1H), 8.00-7.95 (m, 2H), 7.82-7.62 (m, 5H), 7.41-7.35 (m, 2H), 7.19-7.08 (m, 2H), 5.84 (s, 1H), 1.69 (s, 3H), 1.03 (s, 3H). m/z (ESI) 456.1 (M+H)+. The mixture was purged with nitrogen for 5-10 minutes After completion of the reaction (monitored by TLC, TLC system: 30% EtOAc in hexane) the reaction mixture was cooled to ambient temperature filtered through Celite® brand filter aid The filtrate was concentrated purified by column chromatography eluting with 30% EtOAc in hexane

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

Procedure: To a solution of tert-butyl (1-(2-fluorophenyl)-2-hydroxy-2-methylpropyl)carbamate (400 mg, 1.41 mmol) in THF (8 mL) was added potassium tert-butoxide (316.87 mg, 2.82 mmol) at 0-5° C. The resulting reaction mixture was stirred for 2 hours at ambient temperature. After completion of the reaction (monitored by TLC, TLC system: 50% EtOAc in hexane), the reaction mixture was quenched with ice water and extracted with EtOAc. The combined organic layers were washed with, water, saturated NaCl solution and dried on Na2SO4, filtered, and concentrated under reduced pressure to afford 4-(2-fluorophenyl)-5,5-dimethyloxazolidin-2-one (290 mg, 98.18%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.05 (s, 1H), 7.44-7.35 (m, 2H), 7.30-7.22 (m, 2H), 4.88 (s, 1H), 1.53 (s, 3H), 0.88 (s, 3H). m/z (ESI) 210.1 (M+H)+. The resulting reaction mixture the reaction mixture was quenched with ice water extracted with EtOAc The combined organic layers were washed with, water, saturated NaCl solution dried on Na2SO4 filtered concentrated under reduced pressure