2-fluoro-4-(2-hydroxyethyl)benzonitrile

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

Procedure: LiBH4 (1.94 mL, 3.88 mmol, 2 M in THF) was added to a stirred solution of methyl(4-cyano-3-fluorophenyl)acetate (0.50 g, 2.59 mmol) in THF (25 ml) at 0° C. The resulting solution was stirred for 12 h. Water (10 ml) was added, and the resulting solution was extracted with dichloromethane (2×50 ml). The combined organic layers were dried over MgSO4, filtered, and evaporated under reduced pressure. The residue was purified by column chromatography eluting with EtOAc-Hexanes (7:3→1:1) to give the product as colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.60 (dd, J=7.4, J=7.1 Hz, 1H), 7.30 (s, 1H), 7.18 (dd, J=7.3, J=9.1 Hz, 1H), 3.95 (t, J=6.2 Hz, 2H), 2.93 (t, J=6.3 Hz, 2H). the resulting solution was extracted with dichloromethane (2×50 ml) The combined organic layers were dried over MgSO4 filtered evaporated under reduced pressure The residue was purified by column chromatography eluting with EtOAc-Hexanes (7:3→1:1)

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

Procedure: A solution of 2-fluoro-4-(2-hydroxyethyl)benzonitrile (22.5 g, 136 mmol) and MsCl (23.3 g, 205 mmol) in 200 mL of dry DCM was added dropwise TEA (27.5 g, 273 mmol) at 0° C. The resulting mixture was stirred at room temperature overnight before concentrating to dryness. The residue was dissolved in 300 mL of EtOAc and washed with 1 N HCl and brine, dried over anhydrous Na2SO4 and concentrated to afford crude title compound: LC-MS m/z 244 (M+1)+; before concentrating to dryness The residue was dissolved in 300 mL of EtOAc washed with 1 N HCl and brine dried over anhydrous Na2SO4 concentrated

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

Procedure: To a solution of (4-cyano-3-fluorophenyl)acetic acid (25.6 g, 143 mmol) in 150 mL of dry THF was cooled by ice/water, and then BH3/Me2S (10 M, 15.7 mL, 157 mmol) was added slowly. The reaction was warmed to ambient temperature and stirred overnight. The mixture was quenched with MeOH and concentrated to dryness. The residue was partitioned between water and EtOAc. The organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated to afford 2-fluoro-4-(2-hydroxyethyl)benzonitrile. The mixture was quenched with MeOH concentrated to dryness The residue was partitioned between water and EtOAc The organic layers were washed with brine dried over anhydrous sodium sulfate concentrated

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

Procedure: A solution of 2-fluoro-4-(2-hydroxyethyl)benzonitrile (22.5 g, 136 mmol) and MsCl (23.3 g, 205 mmol) in 200 mL of dry DCM was added dropwise TEA (27.5 g, 273 mmol) at 0° C. The resulting mixture was stirred at room temperature overnight before concentrating to dryness. The residue was dissolved in 300 mL of EtOAc and washed with 1 N HCl and brine, dried over anhydrous Na2SO4 and concentrated to afford crude 2-(4-cyano-3-fluorophenyl)ethyl methanesulfonate. MS m/z 244 (M+1)+. before concentrating to dryness The residue was dissolved in 300 mL of EtOAc washed with 1 N HCl and brine dried over anhydrous Na2SO4 concentrated

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

Procedure: To a solution of (4-cyano-3-fluorophenyl)acetic acid (25.6 g, 143 mmol) in 150 mL of dry THF was cooled by ice/water, and then BH3/Me2S (10 M, 15.7 mL, 157 mmol) was added slowly. The reaction was warmed to ambient temperature and stirred overnight. The mixture was quenched with MeOH and concentrated to dryness. The residue was partitioned between water and EtOAc. The organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated to afford 2-fluoro-4-(2-hydroxyethyl)benzonitrile. 1H-NMR (400 MHz, CDCl3) The mixture was quenched with MeOH concentrated to dryness The residue was partitioned between water and EtOAc The organic layers were washed with brine dried over anhydrous sodium sulfate concentrated

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

Procedure: LiBH4 (1.94 mL, 3.88 mmol, 2 M in THF) was added to a stirred solution of methyl(4-cyano-3-fluorophenyl)acetate (0.50 g, 2.59 mmol) in THF (25 ml) at 0° C. The resulting solution was stirred for 12 h. Water (10 ml) was added, and the resulting solution was extracted with dichloromethane (2×50 ml). The combined organic layers were dried over MgSO4, filtered, and evaporated under reduced pressure. The residue was purified by column chromatography eluting with EtOAc-Hexanes (7:3→1:1) to give the product as colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.60 (dd, J=7.4, J=7.1 Hz, 1H), 7.30 (s, 1H), 7.18 (dd, J=7.3, J=9.1 Hz, 1H), 3.95 (t, J=6.2 Hz, 2H), 2.93 (t, J=6.3 Hz, 2H). the resulting solution was extracted with dichloromethane (2×50 ml) The combined organic layers were dried over MgSO4 filtered evaporated under reduced pressure The residue was purified by column chromatography eluting with EtOAc-Hexanes (7:3→1:1)

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

Procedure: A solution of 2-fluoro-4-(2-hydroxyethyl)benzonitrile (22.5 g, 136 mmol) and MsCl (23.3 g, 205 mmol) in 200 mL of dry DCM was added dropwise TEA (27.5 g, 273 mmol) at 0° C. The resulting mixture was stirred at room temperature overnight before concentrating to dryness. The residue was dissolved in 300 mL of EtOAc and washed with 1 N HCl and brine, dried over anhydrous Na2SO4 and concentrated to afford crude 2-(4-cyano-3-fluorophenyl)ethyl methanesulfonate. MS m/z 244 (M+1)+. before concentrating to dryness The residue was dissolved in 300 mL of EtOAc washed with 1 N HCl and brine dried over anhydrous Na2SO4 concentrated

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

Procedure: To a solution of (4-cyano-3-fluorophenyl)acetic acid (25.6 g, 143 mmol) in 150 mL of dry THF was cooled by ice/water, and then BH3/Me2S (10 M, 15.7 mL, 157 mmol) was added slowly. The reaction was warmed to ambient temperature and stirred overnight. The mixture was quenched with MeOH and concentrated to dryness. The residue was partitioned between water and EtOAc. The organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated to afford 2-fluoro-4-(2-hydroxyethyl)benzonitrile. 1H-NMR (400 MHz, CDCl3) δ ppm 7.52˜7.56 (m, 1H), 7.11˜7.15 (m, 2H), 3.89 (t, J=6.3 Hz, 2H), 2.92 (t, J=6.3 Hz, 2H). The mixture was quenched with MeOH concentrated to dryness The residue was partitioned between water and EtOAc The organic layers were washed with brine dried over anhydrous sodium sulfate concentrated