Borane;tetrahydrofuran → (R)-2-bromo-1-pyridin-3-yl-ethanol

Participants

Reaction Conditions

Reaction Steps

A solution of borane-THF (1.0 M solution, 22.8 mL) was added dropwise into a cold (0° C.) solution of (S)-2-methyl-CBS-oxazaborolidine monohydrate (1.12 g, 3.8 mmol) in tetrahydrofuran (20 mL), over a period of 10 minutes. After stirring at 0° C. for 10 minutes, the mixture was added dropwise to a cold (0° C.) suspension of 3-(2-bromoacetyl)pyridine hydrobromide (10.6 g, 38.0 mmol) in tetrahydrofuran (70 mL) over a period of 10 minutes. After the addition the mixture was stirred at room temperature, under a nitrogen atmosphere, overnight. The reaction was cooled to 0° C. and quenched with hydrogen chloride (0.5 M in methanol, 9 mL). The mixture was further diluted with water and extracted with ethyl acetate. The extracts were washed with water and dried with MgSO4. Evaporation and purification by flash column chromatography (dichloromethane/methyl alcohol 95/5) gave (1R)-2-bromo-1-(3-pyridinyl)-1-ethanol as a brown oil (2.01 g, 27% yield). This oil was dissolved in tetrahydrofuran (18 mL) and then sodium hydroxide (5N, 35 mL) was added. The solution was stirred at room temperature for 10 minutes. The mixture was diluted with water and extracted with dichloromethane. The extracts were washed with water, dried with magnesium sulfate. The extracts were concentrated to give the title compound as a white solid (1.01 g, 84% yield); 1H NMR (300 MHz, DMSO-d6) δ 2.93–2.97 (m, 2 H), 3.14–3.17 (m, 2 H), 3.99–4.01 (m, 2 H), 7.36–7.40 (m, 1 H), 7.63–7.66 (m, 1 H), 8.51–8.55 (m, 3 H); MS (ES) m/z: 122 (MH+).

Provenance & Evidence