Borane → (S)-beta-ethyl benzeneethanol

Participants

Reaction Conditions

Reaction Steps

A dry 200 mL Schlenk flask equipped with a magnetic stirrer was cooled to 0° C. and charged with pyrrolidine (1.61 mL, 19.27 mmol, 3.0 equiv) and borane.tetrahydrofuran (1.0M in tetrahydrofuran, 19.27 mL, 19.27 mmol, 3.0 equiv). The mixture was warmed to 23° C. and stirred for 1 hour, before being recooled to 0° C. n-Butyllithium (1.71M in hexanes, 11.27 mL, 19.27 mmol, 3.0 equiv) was added, and the reaction was stirred at 0° C. for 30 minutes. The ice bath was removed, and [1S-[1R*(R*), 2R*]]-α-ethyl-N-(2-hydroxy-1-methyl-2-phenylethyl)-N-methyl benzeneacetamide (1.99 g, 7.21 mmol, 1.0 equiv) was added neat, and the reaction was stirred at 23° C. overnight. The reaction was quenched with aqueous hydrochloric acid, diluted with 1N HCl (300 mL), and extracted with ether (4×60 mL). The ether extracts were washed with 1:1 brine/1N HCl (2×15 mL), and then concentrated. The residue was stirred in 1N NaOH (100 mL) for 30 minutes at 23° C., and extracted with ether (4×25 mL). These ether extracts were washed with 1:1 brine/1N NaOH (2×20 mL),, dried over sodium sulfate, and concentrated. Flash chromatography (40% ether/petroleum ether) of the residue afforded the desired alcohol (819 mg, 85% yield) as a colorless oil: 1H NMR (300 MHz, C6D6) δ7.0-7.2 (m, 5H), 3.48 (m, 2H), 2.44 (m, 1H), 1.58-1.65 (m, 1H), 1.36-1.45 (m, 1H), 0.91 (t, 1H, J=5.3 Hz), 0.72 (t, 3H, J=7.4 Hz); 13C NMR (75.5 MHz, CDCl3) δ: 142.2, 128.6, 128.1, 126.6, 67.3, 50.4, 24.9, 11.9; FTIR (neat film) cm-1: 3354 (br, s), 3028 (m), 2961 (s), 2930 (s), 2874 (s), 1602 (w), 1494 (s), 1454 (s), 1379 (m), 1038 (S), 760 (S), 700 (S).

Provenance & Evidence