3-chloro-1-(4-fluorophenyl)propan-1-ol synthesis

Yield:31736-75-1 82%

Reaction Conditions:

with methanol;sodium tetrahydroborate at 0 - 20; for 1 h;Inert atmosphere;Time;

Steps:

17 INTERMEDIATE 17 PREPARATION OF 3-CHLORO-1-(4-FLUOROPHENYL)PROPAN-1-OL

INTERMEDIATE 17 PREPARATION OF 3-CHLORO-1-(4-FLUOROPHENYL)PROPAN-1-OL NaBH₄ (200 mg, 5.37 mmol) was added portionwise to a solution of 3-chloro-1-(4- fluorophenyl)propan-1-one (1g, 5.37 mmol) in MeOH (10 mL) at 0 °C. The reaction mixture was allowed to reach room temperature and stirred at this temperature for 1 h. A sat. NH₄Cl solution was added and the mixture was stirred at 0 °C for 20 min, then extracted twice with EtOAc. The combined organic phases were dried over Na₂SO₄, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (cyclohexane-EtOAc, 100:0 to 50:50) to afford title compound (830 mg, 82% yield) as colorless oil.¹H NMR (400 MHz, CDCl₃) δ 7.40-7.31 (m, 2H), 7.13- 7.01 (m, 2H), 4.97 (dt, J=8.4, 4.1 Hz, 1H), 3.76 (ddd, J=10.9, 8.3, 5.5 Hz, 1H), 3.57 (dt, J=11.0, 5.9 Hz, 1H), 2.24 (ddt, J=14.4, 8.5, 5.7 Hz, 1H), 2.14- 2.02 (m, 2H). LC-MS (Method A): m/z = 171.0 [M- H₂O]⁺, 0.97 min.

References:

WO2017/96301,2017,A1 Location in patent:Page/Page column 90