2-(4-fluorophenyl)propan-1-ol

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

Procedure: To a solution of 2-(4-fluorophenyl)propanoic acid (1 g, 5.95 mmol) in THF (20 mL) at 0° C. was added 1M BH3.THF (11.89 mL, 11.89 mmol) in THF and the resulting mixture was stirred at room temp for 3 h. Then, 1N HCl (3 mL) was added and the mixture was extracted with ethyl acetate 100 mL), washed with brine (50 mL), dried (Na2SO4), filtered and concentrated. The residue was then purified by Biotage (5-50% EtOAc/hexane) to afford 2-(4-fluorophenyl)propan-1-ol (300 mg, 1.946 mmol, 32.7% yield) as colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.23 (dd, J=8.5, 5.5 Hz, 2H), 7.04 (t, J=8.7 Hz, 2H), 3.79-3.63 (m, 2H), 2.97 (sxt, J=6.9 Hz, 1H), 1.34 (t, J=5.5 Hz, 1H), 1.29 (d, J=7.1 Hz, 3H). the mixture was extracted with ethyl acetate 100 mL), washed with brine (50 mL) dried (Na2SO4) filtered concentrated The residue was then purified by Biotage (5-50% EtOAc/hexane)

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Lithium aluminium hydride (29.8 ml of a 1.0M solution in THF, 29.8 mmol) was added dropwise to a stirred solution of 4-fluoro-α-methylphenyl acetic acid (5.0 g, 29.8 mmol), in diethyl ether (100 ml), which had been cooled to -10° C. The mixture was warmed to +25° C. and stirred for 1 h before quenching with methanol (20 ml) and 4M NaOH (20 ml). The mixture was filtered and the solvent evaporated in vacuo. The residue was chromatographed on silica gel eluting with dichloromethane to give 2-(4-fluorophenyl)propyl alcohol (3.65 g, 79%). To a solution of the preceding alcohol (3.65 g, 23.7 mmol) and carbon tetrabromide (9.82, 29.62 mmol), in dichloromethane (75 ml), was added triphenylphosphine (9.31 g, 35.5 mmol), portionwise. The mixture was stirred for 1 h at room temperature and diethyl ether (50 ml) then added. The precipitated triphenylphosphine oxide was filtered off and the solvents removed in vacuo. The residue was chromatographed through silica gel eluting with ethyl acetate/hexane (1:2) to afford the desired bromide (3.05 g, 60%), δ(250 MHz, CDCl3) 1.40 (3H, d, J=6.8 Hz, Me), 3.06-3.20 (1H, m, CH), 3.42-3.61 (2H, m, CH2), 6.97-7.26 (4H, m, Ar--H). The mixture was warmed to +25° C. before quenching with methanol (20 ml) and 4M NaOH (20 ml) The mixture was filtered the solvent evaporated in vacuo The residue was chromatographed on silica gel eluting with dichloromethane

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

Procedure: To a solution of 2-(4-fluorophenyl)propanoic acid (1 g, 5.95 mmol) in THF (20 mL) at 0° C. was added 1M BH3.THF (11.89 mL, 11.89 mmol) in THF and the resulting mixture was stirred at room temp for 3 h. Then, 1N HCl (3 mL) was added and the mixture was extracted with ethyl acetate 100 mL), washed with brine (50 mL), dried (Na2SO4), filtered and concentrated. The residue was then purified by Biotage (5-50% EtOAc/hexane) to afford 2-(4-fluorophenyl)propan-1-ol (300 mg, 1.946 mmol, 32.7% yield) as colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.23 (dd, J=8.5, 5.5 Hz, 2H), 7.04 (t, J=8.7 Hz, 2H), 3.79-3.63 (m, 2H), 2.97 (sxt, J=6.9 Hz, 1H), 1.34 (t, J=5.5 Hz, 1H), 1.29 (d, J=7.1 Hz, 3H). the mixture was extracted with ethyl acetate 100 mL), washed with brine (50 mL) dried (Na2SO4) filtered concentrated The residue was then purified by Biotage (5-50% EtOAc/hexane)