Acetone → 2-(5-Bromo-3-pyridyl)propan-2-ol

HRID 1521580Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.C([Li])CCC.[CH3:14][C:15]([CH3:17])=[O:16]>C1(C)C=CC=CC=1>[Br:8][C:6]1[CH:7]=[C:2]([C:15]([OH:16])([CH3:17])[CH3:14])[CH:3]=[N:4][CH:5]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a 5000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was added a solution of 3,5-dibromopyridine (264 g, 1.12 mol) in toluene (3000 mL). The solution was cooled to −78° C., and a solution of n-butyllithium in hexanes (2.6 M, 475 mL, 1.24 mol) was then added, giving a solution that was stirred for 2 hours at −78° C. Acetone (108 g, 1.86 mol) was then added. After 1 hour, the reaction mixture was quenched by addition of 350 mL saturated aqueous ammonium chloride solution. The resulting solution was extracted with ethyl acetate. The organic extracts were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash chromatography on silica gel (ethyl acetate/petroleum ether 1:10-1:5) provided the title compound: 1H NMR (400 MHz, CDCl3): δ 8.63 (s, 1H), 8.56 (s, 1H), 8.01 (s, 1H), 1.61 (s, 6H).

Workup

customTo a 5000-mL 4-necked round-bottom flask purged
temperaturemaintained with an inert atmosphere of nitrogen
customgiving a solution that
waitAfter 1 hour
customthe reaction mixture was quenched by addition of 350 mL saturated aqueous ammonium chloride solution
extractionThe resulting solution was extracted with ethyl acetate
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated under reduced pressure
customPurification by flash chromatography on silica gel (ethyl acetate/petroleum ether 1:10-1:5)

Sources & evidence

ORD record: ord-e13c94d91588474b9bd6aa3398dab49d
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073929B2

Reaction notes

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