Sodium hydride → 2-Fluoro-4-iodo-5-[2-[(tetrahydro-2H-pyran-2-yl)oxy]ethoxy]pyridine

HRID 561004Notes

Reaction equation

HRID 561004 reaction equation
[F:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[C:4]([I:9])[CH:3]=1.[H-].[Na+].Br[CH2:13][CH2:14][O:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][O:17]1>CN(C)C=O.C(OCC)(=O)C.O>[F:1][C:2]1[CH:3]=[C:4]([I:9])[C:5]([O:8][CH2:13][CH2:14][O:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)=[CH:6][N:7]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyranHCID 666745926-Fluoro-4-iodopyridin-3-ol

Product 1

HCID 667384442-Fluoro-4-iodo-5-[2-[(tetrahydro-2H-pyran-2-yl)oxy]ethoxy]pyridineYield 75.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Add 6-fluoro-4-iodo-pyridin-3-ol (0.5 g, 2.09 mmol) to a suspension of sodium hydride (60% dispersion in mineral oil, 0.1 g, 2.51 mmol) in dimethylformamide (6 mL). Stir the mixture for 1 hour. Add 2-(2-bromo-ethoxy)-tetrahydro-pyran (0.51 g, 2.34 mmol). Stir the solution at room temperature overnight. Dilute the mixture with ethyl acetate and water. Wash the organic layer with saturated aqueous sodium chloride and water. Dry the mixture over sodium sulfate. Concentrate the solution in vacuo to give yellow oil. Purify the oil by column chromatography (10% ethyl acetate in hexane) to afford the title compound (0.58 g, 75.5%) as a light yellow oil. MS (EI) m/z 368 [M+1]+.

Workup

  1. stirringStir the solution at room temperature overnight
  2. washWash the organic layer with saturated aqueous sodium chloride and water
  3. dry with materialDry the mixture over sodium sulfate
  4. concentrationConcentrate the solution in vacuo
  5. customto give yellow oil
  6. customPurify the oil by column chromatography (10% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-c01a27a2387b424db295d68c774f2d01
Source dataset
uspto-grants-2011_11
Patent number
US08063212B2

Reaction notes

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