Ethyl 1-(hydroxyMethyl)cyclohexanecarboxylate, 97% synthesis

Yield:834914-39-5 71%

Reaction Conditions:

with lithium tri-t-butoxyaluminum hydride in tetrahydrofuran;Reflux;

Steps:

24.1 Step 1: Synthesis of ethyl 1-(hydroxymethyl)cyclohexanecarboxylate (24a)

Diethyl cyclohexane-1,1-dicarboxylate (2.12 g, 9.29 mmol) was dissolved in THF (50 mL) and to which was added LiAl(OtBu)₃ (5.9 g, 23.2 mmol) in portions. The reaction mixture was stirred at reflux overnight. The reaction was cooled in an ice bath and treated carefully with 10% KHSO₄ aq. solution (30 mL) with stirring for 10 min. The precipitate formed was filtered out through a pad of Celite. The filtrate was extracted with EtOAc (3×40 mL) and the organic phase was combined and washed with brine (50 mL), dried over NaSO₄, filtered and concentrated in vacuo. The residue was purified with CombiFlash (SiO₂) in 0-5% MeOH/ DCM to obtain the desired product ( 24) as an oil (1.23 g, 71% yield). ¹H NMR (300 MHz, CDCl₃) δ 4.19 (qd, J=7.1, 0.8 Hz, 2H), 3.62 (d, J=6.4 Hz, 2H), 3.46 (s, 1H), 2.00 (dt, J=11.5, 6.4 Hz, 4H), 1.57-1.22 (m, 9H).

References:

US10085999,2018,B1 Location in patent:Page/Page column 123