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

HRID 1640897Notes

Reaction equation

HRID 1640897 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=O)C.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 DMF (6 mL). Stir the mixture for 1 h. Add 2-(2-bromo-ethoxy)-tetrahydropyran (0.51 g, 2.34 mmol). Stir the solution at RT overnight. Dilute the mixture with ethyl acetate and water. Wash the organic layer with aqueous saturated sodium chloride and water. Dry the mixture over sodium sulfate. Concentrate the solution in vacuo. Purify by column chromatography (10% ethyl acetate in hexane) to afford the title compound (0.58 g, 75.5%) as a light yellow oil. MS (ES) m/z 368 [M+1]+.

Workup

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

Sources & evidence

ORD record
ord-0a17f13cd06b4b2995fa362237b964c9
Source dataset
uspto-grants-2012_02
Patent number
US08114872B2

Reaction notes

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