2-Methylpyridine → HCID 57420359, compound

HRID 1689900Notes

Reaction equation

HRID 1689900 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH3:7].[Li]CCCC.[C:13]([N:20]1[CH2:25][CH2:24][C:23](=[O:26])[CH2:22][CH2:21]1)([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14]>C1COCC1>[C:16]([O:15][C:13]([N:20]1[CH2:25][CH2:24][C:23]([OH:26])([CH2:7][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[CH2:22][CH2:21]1)=[O:14])([CH3:19])([CH3:17])[CH3:18]

Participants

5

Reactant 3

HCID 79752-MethylpyridineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 57420359HCID 57420359, compoundYield 27.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Amine preparation: To a solution of 2-picoline (333 mg) in dry THF (5 mL) at −78° C. was added nBuLi (2.5M solution in hexanes, 1.50 mL). The reaction mixture was warmed to room temperature over 30 min and then cooled to −78° C. 1-BOC-4-piperidone (713 mg) was then added, and the reaction mixture was raised to 0° C. over 20 min. The reaction mixture was stirred overnight and then quenched with water. The organics were extracted into ethyl acetate, dried (MgSO4), filtered and concentrated in vacuo to give crude product. The residue was purified using flash chromatography to yield 4-hydroxy-4-pyridin-2-ylmethyl-piperidine-1-carboxylic acid tert-butyl ester (290 mg). Treatment of this compound with HCl in DCM/MeOH yielded the desired amine, which was isolated as the hydrochloride salt.

Workup

  1. temperaturecooled to −78° C
  2. temperaturethe reaction mixture was raised to 0° C. over 20 min
  3. customquenched with water
  4. extractionThe organics were extracted into ethyl acetate
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give crude product
  9. customThe residue was purified

Sources & evidence

ORD record
ord-ef7d3eb86b3c4331a9e33e04d7012173
Source dataset
uspto-grants-2012_04
Patent number
US08153629B2

Reaction notes

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