[5-bromo-2-(2-methylpyrrolidin-1-yl)phenyl]methanol

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

Procedure: To a solution of sodium hydride (2.84 g, 119 mmol) in anhydrous DMF (80 mL) was added a solution of [5-Bromo-2-(2-methylpyrrolidin-1-yl)phenyl]methanol (16 g, 59.2 mmol) in DMF (50 mL) drop wise at 0° C. After 30 minutes, methyl iodide (7.3 mL, 119 mmol) was added drop wise at 0° C. The reaction mixture was quenched with a saturated aqueous solution of NH4Cl (20 mL), then diluted with water (200 mL) and extracted with EtOAc (150 ml). The organic layer was dried (Na2SO4) and concentrated under reduced pressure to afford the title compound as a yellow oil (16.5 g, 98%). 1H NMR (CDCl3, 400 MHz) δ 7.55 (1H, s), 7.29 (1H, m), 6.86 (1H, d), 4.45 (2H, s), 3.55 (1H, m), 3.41 (1H, m), 2.82 (1H, m), 2.12-2.51 (1H, m), 1.91 (1H, m) 1.81 (1H, m), 1.58 (1H, m), 0.99 (3H, d). The reaction mixture was quenched with a saturated aqueous solution of NH4Cl (20 mL) diluted with water (200 mL) extracted with EtOAc (150 ml) The organic layer was dried (Na2SO4) concentrated under reduced pressure

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

Procedure: To a solution of 5-bromo-2-(2-methylpyrrolidin-1-yl)benzaldehyde (17 g, 63.4 mmol) in methanol (150 mL) under nitrogen was added sodium borohydride (2.41 g, 63.4 mmol) at 0° C. in portions. The reaction mixture was stirred at RT for 1 hour, then evaporated to remove methanol. The resulting crude was taken up with water (250 mL) and extracted with EtOAc (150 mL). The organic layer was washed with water, then dried (Na2SO4) and concentrated under reduced pressure to afford the title compound as a yellow oil (16 g, 93%). 1H NMR (DMSO-d6, 400 MHz) δ 7.53 (1H, d), 7.27 (1H, d), 6.87 (1H, d), 5.22 (1H, t), 4.42 (2H, m), 3.56 (1H, m), 3.36 (1H, m), 2.70 (1H, m), 2.49 (1H, m) 2.09 (1H, m), 1.83 (1H, m), 1.73 (1H, m), 1.47 (1H, m), 0.90 (3H, d). evaporated to remove methanol extracted with EtOAc (150 mL) The organic layer was washed with water dried (Na2SO4) concentrated under reduced pressure

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

Procedure: To a solution of 5-bromo-2-(2-methylpyrrolidin-1-yl)benzaldehyde (17 g, 63.4 mmol) in methanol (150 mL) under nitrogen was added sodium borohydride (2.41 g, 63.4 mmol) at 0° C. in portions. The reaction mixture was stirred at RT for 1 hour, then evaporated to remove methanol. The resulting crude was taken up with water (250 mL) and extracted with EtOAc (150 mL). The organic layer was washed with water, then dried (Na2SO4) and concentrated under reduced pressure to afford the title compound as a yellow oil (16 g, 93%). 1H NMR (DMSO-d6, 400 MHz) δ 7.53 (1H, d), 7.27 (1H, d), 6.87 (1H, d), 5.22 (1H, t), 4.42 (2H, m), 3.56 (1H, m), 3.36 (1H, m), 2.70 (1H, m), 2.49 (1H, m) 2.09 (1H, m), 1.83 (1H, m), 1.73 (1H, m), 1.47 (1H, m), 0.90 (3H, d). evaporated to remove methanol extracted with EtOAc (150 mL) The organic layer was washed with water dried (Na2SO4) concentrated under reduced pressure

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

Procedure: To a solution of 5-bromo-2-(2-methylpyrrolidin-1-yl)benzaldehyde (17 g, 63.4 mmol) in methanol (150 mL) under nitrogen was added sodium borohydride (2.41 g, 63.4 mmol) at 0° C. in portions. The reaction mixture was stirred at RT for 1 hour, then evaporated to remove methanol. The resulting crude was taken up with water (250 mL) and extracted with EtOAc (150 mL). The organic layer was washed with water, then dried (Na2SO4) and concentrated under reduced pressure to afford the title compound as a yellow oil (16 g, 93%). 1H NMR (DMSO-d6, 400 MHz) δ 7.53 (1H, d), 7.27 (1H, d), 6.87 (1H, d), 5.22 (1H, t), 4.42 (2H, m), 3.56 (1H, m), 3.36 (1H, m), 2.70 (1H, m), 2.49 (1H, m) 2.09 (1H, m), 1.83 (1H, m), 1.73 (1H, m), 1.47 (1H, m), 0.90 (3H, d). evaporated to remove methanol extracted with EtOAc (150 mL) The organic layer was washed with water dried (Na2SO4) concentrated under reduced pressure

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

Procedure: To a solution of sodium hydride (2.84 g, 119 mmol) in anhydrous DMF (80 mL) was added a solution of [5-Bromo-2-(2-methylpyrrolidin-1-yl)phenyl]methanol (16 g, 59.2 mmol) in DMF (50 mL) drop wise at 0° C. After 30 minutes, methyl iodide (7.3 mL, 119 mmol) was added drop wise at 0° C. The reaction mixture was quenched with a saturated aqueous solution of NH4Cl (20 mL), then diluted with water (200 mL) and extracted with EtOAc (150 ml). The organic layer was dried (Na2SO4) and concentrated under reduced pressure to afford the title compound as a yellow oil (16.5 g, 98%). 1H NMR (CDCl3, 400 MHz) δ 7.55 (1H, s), 7.29 (1H, m), 6.86 (1H, d), 4.45 (2H, s), 3.55 (1H, m), 3.41 (1H, m), 2.82 (1H, m), 2.12-2.51 (1H, m), 1.91 (1H, m) 1.81 (1H, m), 1.58 (1H, m), 0.99 (3H, d). The reaction mixture was quenched with a saturated aqueous solution of NH4Cl (20 mL) diluted with water (200 mL) extracted with EtOAc (150 ml) The organic layer was dried (Na2SO4) concentrated under reduced pressure

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

Procedure: To a solution of 5-bromo-2-(2-methylpyrrolidin-1-yl)benzaldehyde (17 g, 63.4 mmol) in methanol (150 mL) under nitrogen was added sodium borohydride (2.41 g, 63.4 mmol) at 0° C. in portions. The reaction mixture was stirred at RT for 1 hour, then evaporated to remove methanol. The resulting crude was taken up with water (250 mL) and extracted with EtOAc (150 mL). The organic layer was washed with water, then dried (Na2SO4) and concentrated under reduced pressure to afford the title compound as a yellow oil (16 g, 93%). 1H NMR (DMSO-d6, 400 MHz) δ 7.53 (1H, d), 7.27 (1H, d), 6.87 (1H, d), 5.22 (1H, t), 4.42 (2H, m), 3.56 (1H, m), 3.36 (1H, m), 2.70 (1H, m), 2.49 (1H, m) 2.09 (1H, m), 1.83 (1H, m), 1.73 (1H, m), 1.47 (1H, m), 0.90 (3H, d). evaporated to remove methanol extracted with EtOAc (150 mL) The organic layer was washed with water dried (Na2SO4) concentrated under reduced pressure