(R)-2-Methyl-CBS-oxazaborolidine → (αS)-5-Bromo-α-methyl-2-pyridinemethanol

Temperature

0 °C

The (R)-(+)-2-Methyl-CBS-oxazaborolidine (2.08 g, 7.5 mmol) was dissolved in THF (10 mL), cooled to 0° C. and borane-dimethyl sulfide complex (2 M solution in THF, 7.50 mL, 15.0 mmol, 2.0 equiv.) was added dropwise. The resulting solution was stirred for 1 hour, then cooled to −40° C. and a solution of 1-(5-bromopyridin-2-yl)ethanone in THF (8.0 mL) was added dropwise over 5 min. A white precipitate formed toward the end of the addition. The slurry was stirred for 1 hour, warmed to −10° C., and stirred for another 60 min at this temperature. Analysis of the solution (HPLC) showed >95% conversion to the desired product. The reaction was poured into ethyl acetate (100 mL), washed with saturated ammonium chloride, water, and brine (50 ml each), dried over magnesium sulfate, filtered, and concentrated by rotary evaporation. The residual oil was purified by flash chromatography over silica gel (90 g), eluting with 40% ethyl acetate in hexanes to give the title compound (1.34 g) as a colorless oil.

1. temperaturecooled to −40° C.
2. customA white precipitate formed toward the end of the addition
3. stirringThe slurry was stirred for 1 hour
4. temperaturewarmed to −10° C.
5. stirringstirred for another 60 min at this temperature

ORD record

ord-01c769942bb445f194db657c030b4af1

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09227971B2