2-(4-Fluorophenyl)propionic acid → 2-(4-Fluorophenyl)propan-1-ol

Temperature

-10 °C

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).

1. temperatureThe mixture was warmed to +25° C.
2. custombefore quenching with methanol (20 ml) and 4M NaOH (20 ml)
3. filtrationThe mixture was filtered
4. customthe solvent evaporated in vacuo
5. customThe residue was chromatographed on silica gel eluting with dichloromethane

ORD record

ord-ea5a57131b0740c18293b0402191af72

Source dataset

uspto-grants-1999_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05981529