Sodium hydride → 2-Bromo-5-fluoro-4-((1-methylpiperidin-4-yl)oxy)-3-nitropyridine

HRID 524938Notes

Reaction equation

HRID 524938 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][CH:7]([OH:10])[CH2:6][CH2:5]1.[Br:11][C:12]1[C:17]([N+:18]([O-:20])=[O:19])=[C:16](Br)[C:15]([F:22])=[CH:14][N:13]=1>C1COCC1>[Br:11][C:12]1[C:17]([N+:18]([O-:20])=[O:19])=[C:16]([O:10][CH:7]2[CH2:8][CH2:9][N:4]([CH3:3])[CH2:5][CH2:6]2)[C:15]([F:22])=[CH:14][N:13]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 660484-Piperidinol, 1-methyl-HCID 223090822,4-Dibromo-5-fluoro-3-nitropyridine

Product 1

HCID 867209972-Bromo-5-fluoro-4-((1-methylpiperidin-4-yl)oxy)-3-nitropyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

NaH (86.67 mg, 2.167 mmol) was added portionwise to a solution of 1-methylpiperidin-4-ol (192.0 mg, 1.667 mmol) in THF (5.000 mL) at 0° C. and the resulting solution stirred for 15 min and then 2,4-dibromo-5-fluoro-3-nitro-pyridine (500 mg, 1.667 mmol) in THF (5.000 mL) was added and the reaction mixture stirred at RT overnight. The reaction mixture was partitioned between water (10 mL) and ethyl acetate (10 mL). Combined organic extracts was dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatograph on silica eluting with ethyl acetate/petroleum ether (24 g column, 0-100% EtOAc) using the ISCO column companion system. Product fractions were combined and concentrated in vacuo to leave the product as a yellow oil that solidified on standing. (125 mg). MS (ES+) 334.0 336.0.

Workup

  1. stirringthe reaction mixture stirred at RT overnight
  2. customThe reaction mixture was partitioned between water (10 mL) and ethyl acetate (10 mL)
  3. dry with materialCombined organic extracts was dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatograph on silica eluting with ethyl acetate/petroleum ether (24 g column, 0-100% EtOAc)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7de3f59370dd4b86be02a1a1b99a02f5
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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