Sodium hydride → 1-[4-(5-Bromo-pyridin-3-ylmethoxy)-piperidin-1-yl]-ethanone

HRID 712589Notes

Reaction equation

HRID 712589 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([OH:10])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[H-].[Na+].[Br:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18]([CH2:20]Br)[CH:19]=1>CN(C=O)C>[Br:13][C:14]1[CH:19]=[C:18]([CH2:20][O:10][CH:7]2[CH2:8][CH2:9][N:4]([C:1](=[O:3])[CH3:2])[CH2:5][CH2:6]2)[CH:17]=[N:16][CH:15]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 107492911-(4-Hydroxypiperidin-1-yl)ethan-1-oneHCID 149329483-Bromo-5-(bromomethyl)pyridine

Product 1

HCID 1176670911-[4-(5-Bromo-pyridin-3-ylmethoxy)-piperidin-1-yl]-ethanoneYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cooled (0° C.) solution of 1-acetylpiperidin-4-ol (2.0 g, 14.2 mmol) in DMF (25 mL) is added sodium hydride (60% dispersion in mineral oil, 567 mg, 14.2 mmol). After stifling at 0° C. for 15 min, 3-bromo-5-bromomethyl-pyridine (2.4 g, 9.45 mmol) is added. The reaction is allowed to warm and stir at room temperature for 1 h. The reaction is quenched with the addition of saturated aqueous ammonium chloride and water and is extracted with EtOAc. The combined organic layers are dried (Na2SO4) and concentrated. The crude product is purified by silica gel column (0-10% MeOH in DCM) to provide the title compound (2.1 g).

Workup

  1. temperatureto warm
  2. customThe reaction is quenched with the addition of saturated aqueous ammonium chloride and water
  3. extractionis extracted with EtOAc
  4. dry with materialThe combined organic layers are dried (Na2SO4)
  5. concentrationconcentrated
  6. customThe crude product is purified by silica gel column (0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-06a79ab431114ca7ae0d0857615e7d34
Source dataset
uspto-grants-2015_11
Patent number
US09181272B2

Reaction notes

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