Sodium hydride → 2-[(1-Methyl-4-piperidinyl)oxy]-5-nitropyridine

HRID 1043774Notes

Reaction equation

HRID 1043774 reaction equation
[H-].[Na+].Cl[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][N:5]=1.[CH3:13][N:14]1[CH2:19][CH2:18][CH:17]([OH:20])[CH2:16][CH2:15]1>O1CCCC1>[CH3:13][N:14]1[CH2:19][CH2:18][CH:17]([O:20][C:4]2[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][N:5]=2)[CH2:16][CH2:15]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 660484-Piperidinol, 1-methyl-HCID 783082-Chloro-5-nitropyridine

Product 1

HCID 529048992-[(1-Methyl-4-piperidinyl)oxy]-5-nitropyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of sodium hydride (189 mg, 4.73 mmol) in anhydrous tetrahydrofuran (2 mL) at 0° C., a solution of 2-chloro-5-nitropyridine (500 mg, 3.16 mmol) and 1-methylpiperidin-4-ol (455 mg, 3.96 mmol) in anhydrous tetrahydrofuran (4 mL) was added dropwise. The reaction was heated reflux for 16 h. The THF was evaporated and water (100 mL) and EtOAc (200 mL) were added. The aqueous layer was extracted with EtOAc (200 mL). The organic layers were combined, washed with brine, dried over sodium sulfate and concentrated to give a brown oil. Purification by silica gel column chromatography using 3% methanol/methylene chloride yielded 2-(1-methylpiperidin-4-yloxy)-5-nitropyridine as a yellow solid, (367 mg, 49%). LC/MS (m/z): 238.0 (MH+), Rt 1.59 minutes.

Workup

  1. temperatureThe reaction was heated
  2. temperaturereflux for 16 h
  3. customThe THF was evaporated
  4. additionwater (100 mL) and EtOAc (200 mL) were added
  5. extractionThe aqueous layer was extracted with EtOAc (200 mL)
  6. washwashed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customto give a brown oil
  10. customPurification by silica gel column chromatography

Sources & evidence

ORD record
ord-6a3be33026c146619f11352d6a97716c
Source dataset
uspto-grants-2013_10
Patent number
US08563549B2

Reaction notes

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