Citric Acid → HCID 59824996, compound

Temperature

-78 °C

25 mL of anhydrous THF was placed under nitrogen and cooled to −78° C. 2.2 ml (5.5 mmol) of a 2.5 M solution of n-butyl lithium in hexanes were added. To the resulting solution was slowly added 0.7 mL (1.4 g, 5.8 mmol) of 1,3-dibromobenzene. Upon complete addition the resulting solution was stirred at −78° C. for 90 min. 1.00 g (5.71 mmol) of 3-trifluoromethyl-pyridine-2-carbaldehyde was added rapidly. The dark solution was warmed to −20° C. and stirred for 20 min at that temperature. The resulting mixture was distributed between 10% aqueous citric acid and dichloromethane. The phases were separated and the aqueous layer extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and the solvent completely evaporated. The resulting residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes to afford 1.053 g (3.171 mmol, 58%) of (3-bromo-phenyl)-(3-trifluoromethyl-pyridin-2-yl)-methanol as a yellow oil. 1H NMR (500 MHz, DMSO-d6) δ 8.84 (m, 1H), 8.18 (dd, 1H), 7.63 (m, 1H), 7.53 (dd, 1H), 7.42 (m, 1H), 7.26-7.24 (m, 2H), 6.31 (d, 1H), 6.02 (d, 1H); MS: m/z 332.0+334.0 (M+H+).

1. additionUpon complete addition the resulting solution
2. temperatureThe dark solution was warmed to −20° C.
3. stirringstirred for 20 min at that temperature
4. customThe phases were separated
5. extractionthe aqueous layer extracted three times with dichloromethane
6. dry with materialThe combined organic phases were dried over sodium sulfate
7. customthe solvent completely evaporated
8. customThe resulting residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes

ORD record

ord-ddc32d20e86b47a88d4ee59ba4bd20b2

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08242280B2