Imidazole → (R)-3-(2-Bromo-1-(tert-butyl-dimethyl-silanyl)-ethyl)-pyridine

To a stirred solution of 1.54 g (7.61 mmol) of (R)-2-bromo-1-pyridin-3-yl-ethanol l-1 in 20 ml of dry N,N-dimethylformamide at room temperature was added 1.55 g (22.83 mmol) of imidazole followed by 1.72 g (11.4 mmol) of tert-butyldimethylsilyl chloride. The mixture was stirred at room temperature for about 18 hours and then an additional 1.55 g (22.83 mmol) of imidazole and 1.72 g (11.4 mmol) of tert-butyldimethylsilyl chloride were added, and the mixture was stirred at room temperature for about an additional 24 hours. The mixture was poured into 200 ml of water and extracted with ethyl acetate (2×200 ml). The organic extracts were combined, washed successively with water (1×40 ml), brine (1×40 ml), then dried over magnesium sulfate and concentrated in vacuo to furnish an oil. Chromatography on silica gel eluting with ethyl acetate:hexanes (2:3, v/v) provided 1.41 g (58% yield) of the desired title compound as a clear oil, αD=−51.5° (c=0.60, chloroform). Chiral HPLC analysis of the product on 4.6×250 mm Chiralcel® OD column (Chiral Technologies; Exton, Pa.) eluting with hexanes:isopropyl alcohol (7:3, v/v) at 1.0 ml/minute revealed an enantiomeric excess of 91.3%.

1. stirringthe mixture was stirred at room temperature for about an additional 24 hours
2. extractionextracted with ethyl acetate (2×200 ml)
3. washwashed successively with water (1×40 ml), brine (1×40 ml)
4. dry with materialdried over magnesium sulfate
5. concentrationconcentrated in vacuo
6. customto furnish an oil

ORD record

ord-9f80643b3ea04ef5b689bbdf2d62e607

Source dataset

uspto-grants-2004_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06689800B2