Cesium carbonate → 2-Fluoro-5-(2-methoxyethoxy)pyridine

HRID 876495Notes

Reaction equation

HRID 876495 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].[F:7][C:8]1[N:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1.Br[CH2:16][CH2:17][O:18][CH3:19]>CN(C=O)C>[F:7][C:8]1[CH:9]=[CH:10][C:11]([O:14][CH2:16][CH2:17][O:18][CH3:19])=[CH:12][N:13]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 809722-Bromoethyl methyl etherHCID 27631086-Fluoropyridin-3-ol

Product 1

HCID 666002752-Fluoro-5-(2-methoxyethoxy)pyridineYield 92.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a 0° C. suspension of Cs2CO3 (18.73 g, 57.48 mmol) in 150 mL DMF was added 6-fluoropyridin-3-ol (5.0 g, 44.21 mmol). The cloudy brown mixture was stirred for 15 minutes, then 1-bromo-2-methoxyethane (6.232 mL, 66.32 mmol) was added. The reaction mixture was heated in a 110° C. sand bath and stirred for 17 hours, after which it was cooled to ambient temperature and the DMF was removed in vacuo. The resulting residue was combined with saturated NH4Cl and the mixture was extracted with DCM. The combined extracts were dried (Na2SO4), filtered, and concentrated. The crude material was purified on silica gel (5-50% ethyl acetate in hexanes gradient) to give the desired product (7.00 g, 92.50% yield) as a clear, colorless oil.

Workup

  1. stirringstirred for 17 hours
  2. temperatureafter which it was cooled to ambient temperature
  3. customthe DMF was removed in vacuo
  4. extractionthe mixture was extracted with DCM
  5. dry with materialThe combined extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified on silica gel (5-50% ethyl acetate in hexanes gradient)

Sources & evidence

ORD record
ord-50f493e6e8334026b254c5813bcd12c0
Source dataset
uspto-grants-2015_03
Patent number
US08987251B2

Reaction notes

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