2-Bromopyridine → tert-Butyl 4-[hydroxy(pyridin-2-yl)methyl]piperidine-1-carboxylate

HRID 412894Notes

Reaction equation

HRID 412894 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])CCC.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([CH:26]=[O:27])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]>CCOCC>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([CH:26]([OH:27])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 79732-BromopyridineHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 18539092tert-Butyl 4-[hydroxy(pyridin-2-yl)methyl]piperidine-1-carboxylateYield 62%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of 2-bromopyridine (488 μL, 5 mmol) in ether (10 mL) was added dropwise butyl lithium (1.6M hexane solution, 3.125 mL, 5 mmol) at −78° C., and the mixture was stirred for 30 minutes. To the mixture was added dropwise a solution of 1-tert-butoxycarbonyl-4-formylpiperidine (1066 mg, 5 mmol) in ether (10 mL) at −78° C. The mixture was stirred for 18 hours while the temperature is elevated to room temperature. The reaction mixture was washed with saturated aqueous solution of sodium hydrogencarbonate and saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography (ethyl acetate:hexane=1:2) to give the titled compound as yellowish oily substance (913 mg). Yield 62%.

Workup

  1. stirringThe mixture was stirred for 18 hours while the temperature
  2. customis elevated to room temperature
  3. washThe reaction mixture was washed with saturated aqueous solution of sodium hydrogencarbonate and saturated aqueous solution of sodium chloride
  4. dry with materialdried over magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe residue was purified by column chromatography (ethyl acetate:hexane=1:2)

Sources & evidence

ORD record
ord-bc68ff9b117b4c3a9dae0cb6b95aabb2
Source dataset
uspto-grants-2003_05
Patent number
US06562978B1

Reaction notes

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