Water → 5-Bromo-2-(methylthio)pyridine

HRID 906832Notes

Reaction equation

HRID 906832 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[CH3:9][S-:10].[Na+].O.C(OCC)(=O)C>CN(C)C=O>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([S:10][CH3:9])=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 693532,5-DibromopyridineHCID 4378561Sodium methanethiolate

Product 1

HCID 114242515-Bromo-2-(methylthio)pyridineYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

2,5-Dibromo-pyridine (3.0 g, 12.7 mmol) and sodium thiomethoxide (0.84 g, 12 mmol) were dissolved in 18 ml anhydrous N,N-dimethylformamide. The mixture was heated at 160° C. under nitrogen for 6 hrs. After cooling to ambient temperature, water and ethyl acetate were added to the reaction mixture. The aqueous layer was extracted with ethyl acetate several times. The combined extract was washed with brine, dried over sodium sulfate, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (0→6% EtOAC/Hexane) to give 5-bromo-2-methylsulfanyl-pyridine as a white solid (2.18 g, 84% yield). 1H-NMR (400 MHz, CDCl3): δ 2.55 (s, 3H), 7.09 (dd, 1H, J=0.7, J=8.6), 7.59 (dd, 1H, J=2.4, J=8.6), 8.50 (m, 1H).

Workup

  1. temperatureAfter cooling to ambient temperature
  2. extractionThe aqueous layer was extracted with ethyl acetate several times
  3. extractionThe combined extract
  4. washwas washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography on silica gel (0→6% EtOAC/Hexane)

Sources & evidence

ORD record
ord-29fc5c50b70a4a90a9ab159c07d7938c
Source dataset
uspto-grants-2011_09
Patent number
US08013001B2

Reaction notes

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