2-(5-bromo-2-fluorophenyl)propan-2-ol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(5-bromo-2-fluoro-phenyl)-propan-2-ol (119.7 g, 498 mmol) in CH2Cl2 (50 ml) was added hydrochinone (2.74 g, 24.9 mmol) and 250 ml 85% H3PO4. The resulting reaction mixture was stirred for 3.5 h at 50° C. The mixture was poured onto ice-water and extracted with CH2Cl2. The organic phases were washed with 2N aqueous NaOH and water, dried over MgSO4, filtered and concentrated. The crude product was dissolved in hexane and filtered through a plough of silica gel to obtain after concentration at 600 mbar the title compound as a colorless oil: TLC (hexane): Rf=0.52; HPLC RtH5=1.416 min; 1H NMR (360 MHz, CDCl3): δ 7.43 (dd, 1H), 7.37 (m, 1H), 6.94 (dd, 1H), 5.27 (d, 2H), 2.13 (s, 3H). The resulting reaction mixture The mixture was poured onto ice-water extracted with CH2Cl2 The organic phases were washed with 2N aqueous NaOH and water dried over MgSO4 filtered concentrated The crude product was dissolved in hexane filtered through a plough of silica gel to obtain after concentration at 600 mbar the title compound as a colorless oil HPLC RtH5=1.416 min

反応条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of diisopropyl amine (57.3 ml, 402 mmol) in THF (500 ml) was added under argon a 1.6 M solution of nBuLi in hexane (260 ml, 416 mmol) below −50° C. After stirring for 30 min at −75° C., 4-bromo-1-fluoro benzene (31.1 ml, 277 mmol) was added while keeping the temperature below −70° C. After stirring for 2 h at −75° C., acetone (41.2 ml, 554 mmol) was added below −65° C. and the reaction mixture was stirred for 1 h at −75° C., warmed up to −50° C. and poured onto 10% aqueous NH4Cl solution. The mixture was extracted with TBME, organic phases were washed with aqueous KHSO4 solution, saturated NaHCO3 solution and brine, dried over MgSO4, filtered and concentrated. The crude product was crystallized from hexane to provide the title compound as white crystals: TLC (hexane-EtOAc 3:1): Rf=0.45; HPLC RtH5=1.045 min; 1H NMR (360 MHz, CDCl3): δ 7.74 (dd, 1H), 7.36 (m, 1H), 6.93 (dd, 1H), 2.04 (d, 1H), 1.63 (s, 61-1). the temperature below −70° C After stirring for 2 h at −75° C. the reaction mixture was stirred for 1 h at −75° C. warmed up to −50° C. The mixture was extracted with TBME, organic phases were washed with aqueous KHSO4 solution, saturated NaHCO3 solution and brine dried over MgSO4 filtered concentrated The crude product was crystallized from hexane

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(5-bromo-2-fluoro-phenyl)-propan-2-ol (119.7 g, 498 mmol) in CH2Cl2 (50 ml) was added hydrochinone (2.74 g, 24.9 mmol) and 250 ml 85% H3PO4. The resulting reaction mixture was stirred for 3.5 h at 50° C. The mixture was poured onto ice-water and extracted with CH2Cl2. The organic phases were washed with 2N aqueous NaOH and water, dried over MgSO4, filtered and concentrated. The crude product was dissolved in hexane and filtered through a plough of silica gel to obtain after concentration at 600 mbar the title compound as a colorless oil: TLC (hexane): Rf=0.52; UPLC RtH5=1.416 min; 1H NMR (360 MHz, CDCl3): δ 7.43 (dd, 1H), 7.37 (m, 1H), 6.94 (dd, 1H), 5.27 (d, 2H), 2.13 (s, 3H). The resulting reaction mixture The mixture was poured onto ice-water extracted with CH2Cl2 The organic phases were washed with 2N aqueous NaOH and water dried over MgSO4 filtered concentrated The crude product was dissolved in hexane filtered through a plough of silica gel to obtain after concentration at 600 mbar the title compound as a colorless oil UPLC RtH5=1.416 min

反応条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of diisopropyl amine (57.3 ml, 402 mmol) in THF (500 ml) was added under argon a 1.6 M solution of nBuLi in hexane (260 ml, 416 mmol) below −50° C. After stirring for 30 min at −75° C., 4-bromo-1-fluoro benzene (31.1 ml, 277 mmol) was added while keeping the temperature below −70° C. After stirring for 2 h at −75° C., acetone (41.2 ml, 554 mmol) was added below −65° C. and the reaction mixture was stirred for 1 h at −75° C., warmed up to −50° C. and poured onto 10% aqueous NH4Cl solution. The mixture was extracted with TBME, organic phases were washed with aqueous KHSO4 solution, saturated NaHCO3 solution and brine, dried over MgSO4, filtered and concentrated. The crude product was crystallized from hexane to provide the title compound as white crystals: TLC (hexane-EtOAc 3:1): Rf=0.45; UPLC RtH5=1.045 min; 1H NMR (360 MHz, CDCl3): δ 7.74 (dd, 1H), 7.36 (m, 1H), 6.93 (dd, 1H), 2.04 (d, 1H), 1.63 (s, 6H). the temperature below −70° C After stirring for 2 h at −75° C. the reaction mixture was stirred for 1 h at −75° C. warmed up to −50° C. The mixture was extracted with TBME, organic phases were washed with aqueous KHSO4 solution, saturated NaHCO3 solution and brine dried over MgSO4 filtered concentrated The crude product was crystallized from hexane

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(5-bromo-2-fluoro-phenyl)-propan-2-ol (119.7 g, 498 mmol) in CH2Cl2 (50 ml) was added hydrochinone (2.74 g, 24.9 mmol) and 250 ml 85% H3PO4. The resulting reaction mixture was stirred for 3.5 h at 50° C. The mixture was poured onto ice-water and extracted with CH2Cl2. The organic phases were washed with 2N aqueous NaOH and water, dried over MgSO4, filtered and concentrated. The crude product was dissolved in hexane and filtered through a plough of silica gel to obtain after concentration at 600 mbar the title compound as a colorless oil: TLC (hexane): Rf=0.52; HPLC RtH5=1.416 min; 1H NMR (360 MHz, CDCl3): δ 7.43 (dd, 1H), 7.37 (m, 1H), 6.94 (dd, 1H), 5.27 (d, 2H), 2.13 (s, 3H). The resulting reaction mixture The mixture was poured onto ice-water extracted with CH2Cl2 The organic phases were washed with 2N aqueous NaOH and water dried over MgSO4 filtered concentrated The crude product was dissolved in hexane filtered through a plough of silica gel to obtain after concentration at 600 mbar the title compound as a colorless oil HPLC RtH5=1.416 min

反応条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of diisopropyl amine (57.3 ml, 402 mmol) in THF (500 ml) was added under argon a 1.6 M solution of nBuLi in hexane (260 ml, 416 mmol) below −50° C. After stirring for 30 min at −75° C., 4-bromo-1-fluoro benzene (31.1 ml, 277 mmol) was added while keeping the temperature below −70° C. After stirring for 2 h at −75° C., acetone (41.2 ml, 554 mmol) was added below −65° C. and the reaction mixture was stirred for 1 h at −75° C., warmed up to −50° C. and poured onto 10% aqueous NH4Cl solution. The mixture was extracted with TBME, organic phases were washed with aqueous KHSO4 solution, saturated NaHCO3 solution and brine, dried over MgSO4, filtered and concentrated. The crude product was crystallized from hexane to provide the title compound as white crystals: TLC (hexane-EtOAc 3:1): Rf=0.45; HPLC RtH5=1.045 min; 1H NMR (360 MHz, CDCl3): δ 7.74 (dd, 1H), 7.36 (m, 1H), 6.93 (dd, 1H), 2.04 (d, 1H), 1.63 (s, 61-1). the temperature below −70° C After stirring for 2 h at −75° C. the reaction mixture was stirred for 1 h at −75° C. warmed up to −50° C. The mixture was extracted with TBME, organic phases were washed with aqueous KHSO4 solution, saturated NaHCO3 solution and brine dried over MgSO4 filtered concentrated The crude product was crystallized from hexane

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(5-bromo-2-fluoro-phenyl)-propan-2-ol (119.7 g, 498 mmol) in CH2Cl2 (50 ml) was added hydrochinone (2.74 g, 24.9 mmol) and 250 ml 85% H3PO4. The resulting reaction mixture was stirred for 3.5 h at 50° C. The mixture was poured onto ice-water and extracted with CH2Cl2. The organic phases were washed with 2N aqueous NaOH and water, dried over MgSO4, filtered and concentrated. The crude product was dissolved in hexane and filtered through a plough of silica gel to obtain after concentration at 600 mbar the title compound as a colorless oil: TLC (hexane): Rf=0.52; UPLC RtH5=1.416 min; 1H NMR (360 MHz, CDCl3): δ 7.43 (dd, 1H), 7.37 (m, 1H), 6.94 (dd, 1H), 5.27 (d, 2H), 2.13 (s, 3H). The resulting reaction mixture The mixture was poured onto ice-water extracted with CH2Cl2 The organic phases were washed with 2N aqueous NaOH and water dried over MgSO4 filtered concentrated The crude product was dissolved in hexane filtered through a plough of silica gel to obtain after concentration at 600 mbar the title compound as a colorless oil UPLC RtH5=1.416 min

反応条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of diisopropyl amine (57.3 ml, 402 mmol) in THF (500 ml) was added under argon a 1.6 M solution of nBuLi in hexane (260 ml, 416 mmol) below −50° C. After stirring for 30 min at −75° C., 4-bromo-1-fluoro benzene (31.1 ml, 277 mmol) was added while keeping the temperature below −70° C. After stirring for 2 h at −75° C., acetone (41.2 ml, 554 mmol) was added below −65° C. and the reaction mixture was stirred for 1 h at −75° C., warmed up to −50° C. and poured onto 10% aqueous NH4Cl solution. The mixture was extracted with TBME, organic phases were washed with aqueous KHSO4 solution, saturated NaHCO3 solution and brine, dried over MgSO4, filtered and concentrated. The crude product was crystallized from hexane to provide the title compound as white crystals: TLC (hexane-EtOAc 3:1): Rf=0.45; UPLC RtH5=1.045 min; 1H NMR (360 MHz, CDCl3): δ 7.74 (dd, 1H), 7.36 (m, 1H), 6.93 (dd, 1H), 2.04 (d, 1H), 1.63 (s, 6H). the temperature below −70° C After stirring for 2 h at −75° C. the reaction mixture was stirred for 1 h at −75° C. warmed up to −50° C. The mixture was extracted with TBME, organic phases were washed with aqueous KHSO4 solution, saturated NaHCO3 solution and brine dried over MgSO4 filtered concentrated The crude product was crystallized from hexane

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(5-bromo-2-fluoro-phenyl)-propan-2-ol (119.7 g, 498 mmol) in CH2Cl2 (50 ml) was added hydrochinone (2.74 g, 24.9 mmol) and 250 ml 85% H3PO4. The resulting reaction mixture was stirred for 3.5 h at 50° C. The mixture was poured onto ice-water and extracted with CH2Cl2. The organic phases were washed with 2N aqueous NaOH and water, dried over MgSO4, filtered and concentrated. The crude product was dissolved in hexane and filtered through a plough of silica gel to obtain after concentration at 600 mbar the title compound as a colorless oil: TLC (hexane): Rf=0.52; UPLC RtH5=1.416 min; 1H NMR (360 MHz, CDCl3): δ 7.43 (dd, 1H), 7.37 (m, 1H), 6.94 (dd, 1H), 5.27 (d, 2H), 2.13 (s, 3H). The resulting reaction mixture The mixture was poured onto ice-water extracted with CH2Cl2 The organic phases were washed with 2N aqueous NaOH and water dried over MgSO4 filtered concentrated The crude product was dissolved in hexane filtered through a plough of silica gel to obtain after concentration at 600 mbar the title compound as a colorless oil UPLC RtH5=1.416 min

反応条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of diisopropyl amine (57.3 ml, 402 mmol) in THF (500 ml) was added under argon a 1.6 M solution of nBuLi in hexane (260 ml, 416 mmol) below −50° C. After stirring for 30 min at −75° C., 4-bromo-1-fluoro benzene (31.1 ml, 277 mmol) was added while keeping the temperature below −70° C. After stirring for 2 h at −75° C., acetone (41.2 ml, 554 mmol) was added below −65° C. and the reaction mixture was stirred for 1 h at −75° C., warmed up to −50° C. and poured onto 10% aqueous NH4Cl solution. The mixture was extracted with TBME, organic phases were washed with aqueous KHSO4 solution, saturated NaHCO3 solution and brine, dried over MgSO4, filtered and concentrated. The crude product was crystallized from hexane to provide the title compound as white crystals: TLC (hexane-EtOAc 3:1): Rf=0.45; UPLC RtH5=1.045 min; 1H NMR (360 MHz, CDCl3): δ 7.74 (dd, 1H), 7.36 (m, 1H), 6.93 (dd, 1H), 2.04 (d, 1H), 1.63 (s, 6H). the temperature below −70° C After stirring for 2 h at −75° C. the reaction mixture was stirred for 1 h at −75° C. warmed up to −50° C. The mixture was extracted with TBME, organic phases were washed with aqueous KHSO4 solution, saturated NaHCO3 solution and brine dried over MgSO4 filtered concentrated The crude product was crystallized from hexane