Borane → (S)-beta-ethyl benzeneethanol

Temperature

0 °C

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).

1. customA dry 200 mL Schlenk flask equipped with a magnetic stirrer
2. temperatureThe mixture was warmed to 23° C.
3. custombefore being recooled to 0° C.
4. additionwas added
5. stirringthe reaction was stirred at 0° C. for 30 minutes
6. customThe ice bath was removed
7. stirringthe reaction was stirred at 23° C. overnight
8. customThe reaction was quenched with aqueous hydrochloric acid
9. additiondiluted with 1N HCl (300 mL)
10. extractionextracted with ether (4×60 mL)
11. washThe ether extracts were washed with 1:1 brine/1N HCl (2×15 mL)
12. concentrationconcentrated
13. stirringThe residue was stirred in 1N NaOH (100 mL) for 30 minutes at 23° C.
14. extractionextracted with ether (4×25 mL)
15. washThese ether extracts were washed with 1:1 brine/1N NaOH (2×20 mL)
16. dry with materialdried over sodium sulfate
17. concentrationconcentrated

ORD record

ord-1d5c85af55ea4f99b26722a350b8c8d6

Source dataset

uspto-grants-1996_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05488131