Yield:1195945-17-5 99%

Reaction Conditions:

with lithium aluminium tetrahydride in tetrahydrofuran at 0; for 5 h;Inert atmosphere;Reflux;

Steps:

47 (2R,3R,4R,5S)-1-(5-chloro-2-fluorophenethyl)-2-methylpiperidine-3,4,5-triol

To a cooled (0 °C) solution of 2-(5-chloro-2-fluorophenyl)acetic acid (0.5 g, 2.6 mmol) in 15 mL of anhydrous THF, LAH (0.3 g, 8.7 mmol) was added portionwise while stirring, under Ar. When effervescence ceased, the mixture was heated at reflux for 5 h until disappearance of starting material. The mixture was diluted with EtOAc, washed with 1.0 M HCl, water and brine. The organics were dried over anhydrous Na₂SO₄ and concentrated to 2-(5-chloro-2-fluorophenyl) ethanol (0.46 g, 99%) as an oil. ¹H NMR (400 MHz, CDCl3) d 7.22 (dd, J = 6.5, 2.7 Hz, 1H), 7.15 (dddd, J = 8.4, 4.2, 2.7, 0.9 Hz, 1H), 6.99-6.92 (m, 1H), 3.81 (td, J = 6.6, 2.4 Hz, 2H), 2.84 (td, J = 6.6, 3.2 Hz, 2H), 2.26 (bs, 1H).

References:

WO2020/229968,2020,A1 Location in patent:Paragraph 00256