Water → 2-(2,5-Dimethylpyrrolyl)-6(4-((n-benzyl)-4-piperidinyloxy)-naphth-1-yl)pyridine

HRID 1743999Notes

Reaction equation

HRID 1743999 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.[H-].[Na+].[CH3:17][C:18]1[NH:19][C:20]([CH3:40])=[CH:21][C:22]=1[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32](F)=[CH:31][CH:30]=2)[N:24]=1.O>CN(C)C=O>[CH3:17][C:18]1[NH:19][C:20]([CH3:40])=[CH:21][C:22]=1[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]([O:1][CH:2]3[CH2:7][CH2:6][N:5]([CH2:8][C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=4)[CH2:4][CH2:3]3)=[CH:31][CH:30]=2)[N:24]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 784611-Benzylpiperidin-4-olHCID 543666152-(2,5-Dimethylpyrrolyl)-6-(4-fluoro-naphth-1-yl)pyridine

Product 1

HCID 541214482-(2,5-Dimethylpyrrolyl)-6(4-((n-benzyl)-4-piperidinyloxy)-naphth-1-yl)pyridineYield 317.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

To a 20 mL round-bottomed flask equipped with condenser and N2 inlet were added 121 mg (0.633 mml) 4-hydroxy-N-benzylpiperidine and 5 mL dry dimethylformamide, followed by 32 mg (0.791 mmol) sodium hydride (60% in oil). The reaction was heated to 70° C. to ensure complete formation of the alkoxide, and then 100 mg (0.316 mmol) 2-(2,5-dimethylpyrrolyl)-6-(4-fluoro-naphth-1-yl)pyridine in 2 mL dry dimethylformamide was added, and the reaction was heated at 80° C. for 10 min. The reaction was cooled, poured into water, and extracted into ethyl acetate. After combining with another run on a larger scale, the combined organic layer was washed with brine, dried over sodium sulfate, and evaporated. The residue was chromatographed on silica gel using methanol/methylene chloride as eluant to afford 489 mg (54%) of an oil.

Workup

  1. customTo a 20 mL round-bottomed flask equipped with condenser and N2 inlet
  2. temperaturethe reaction was heated at 80° C. for 10 min
  3. temperatureThe reaction was cooled
  4. extractionextracted into ethyl acetate
  5. washthe combined organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. customevaporated
  8. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-3b7ca73ce271499b803a1baf61a79d3d
Source dataset
uspto-grants-2006_03
Patent number
US07012078B2

Reaction notes

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