2,5-Dibromopyridine → HCID 131735893, compound

HRID 2207369Notes

Reaction equation

HRID 2207369 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[Li]CCCC.[Si:14]([O:21][CH2:22][C:23](=[O:25])[CH3:24])([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]>C1(C)C=CC=CC=1>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C:23]([OH:25])([CH3:24])[CH2:22][O:21][Si:14]([C:17]([CH3:19])([CH3:18])[CH3:20])([CH3:15])[CH3:16])=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 693532,5-Dibromopyridine2×HCID 41249691-(tert-Butyldimethylsilyloxy)-2-propanoneHCID 178418339Butyllithium

Product 1

HCID 131735893HCID 131735893, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-78 °C

Procedure

For a literature procedure to carry out a selective mono-lithiation of 2,5-dibromopyridine, see: Wang, X.; Rabbat, P.; O'Shea, P.; Tillyer, R.; Grabowski, E. J. J.; Reider, P. J. Tetrahedron Lett. 2000, 41, 4335-4338. n-BuLi (3.17 mL, 5.07 mmol) was added to 2,5-dibromopyridine (1.00 g, 4.22 mmol) in toluene (49.7 mL) at −78° C. and stirred for 2 hours at −78° C. 1-{[tert-Butyl(dimethyl)silyl]oxy}propan-2-one (1.22 mL, 6.33 mmol) was added dropwise to the reaction mixture over 15 minutes. Upon addition, the reaction mixture was warmed to room temperature overnight. The reaction mixture was quenched with a saturated aqueous NH4Cl (2.00 mL) and the solvent was removed under reduced pressure. The resultant residue was diluted with dichloromethane (20.0 mL) and was partitioned with a saturated aqueous solution of NH4Cl (20.0 mL). The organic layer was dried over sodium sulfate, concentrated under reduced pressure and purified by silica gel chromatography (ethyl acetate/hexanes) to yield 2-(5-bromopyridin-2-yl)-1-{[tert-butyl(dimethyl)silyl]oxy}propan-2-ol. MS APCI calc'd for C14H25BrNO2Si [M+H]+ 346. found 346 and 348.

Workup

  1. additionUpon addition
  2. temperaturethe reaction mixture was warmed to room temperature overnight
  3. customThe reaction mixture was quenched with a saturated aqueous NH4Cl (2.00 mL)
  4. customthe solvent was removed under reduced pressure
  5. additionThe resultant residue was diluted with dichloromethane (20.0 mL)
  6. customwas partitioned with a saturated aqueous solution of NH4Cl (20.0 mL)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. custompurified by silica gel chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-a49be9cd0d9144918632ec9255d3bf69
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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