Diethyl Ether → Tert-butyl 4-hydroxy-4-(pyridin-2-YL)piperidine-1-carboxylate

HRID 881537Notes

Reaction equation

HRID 881537 reaction equation
[Li]CCCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.[C:13]([N:20]1[CH2:25][CH2:24][CH2:23][CH2:22][C:21]1=O)([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].CC[O:29]CC>>[C:16]([O:15][C:13]([N:20]1[CH2:25][CH2:24][C:23]([OH:29])([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[CH2:22][CH2:21]1)=[O:14])([CH3:19])([CH3:18])[CH3:17]

Participants

5

Reactant 4

HCID 3283Diethyl EtherHCID 79732-BromopyridineHCID 7577838tert-Butyl 2-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 11948569Tert-butyl 4-hydroxy-4-(pyridin-2-YL)piperidine-1-carboxylate

Procedure

To a solution of nBuLi (2.5 m in hexanes, 2.00 mL) at −50° C. was added 2-bromopyridine (780 mg) in dry ether (10 mL). After 10 minutes an ethereal solution of BOC-piperidone (1.16 g) was added and the reaction mixture was gradually warmed to room temperature. After 1 hour, the reaction mixture was quenched with ammonium chloride solution, extracted with ether, dried (MgSO4) and the solvent removed in vacuo to yield an oil which was purified using flash chromatography to yield 4′-Hydroxy-3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester. Cleavage of the BOC group with HCl yielded 2′,3′,5′,6′-tetrahydro-1′H-[2,4]bipyridinyl-4′-ol.

Workup

  1. customthe reaction mixture was quenched with ammonium chloride solution
  2. extractionextracted with ether
  3. dry with materialdried (MgSO4)
  4. customthe solvent removed in vacuo
  5. customto yield an oil which
  6. customwas purified

Sources & evidence

ORD record
ord-5d69fc3cc19f4cfa907802c2f021c00b
Source dataset
uspto-grants-2015_03
Patent number
US08993563B2

Reaction notes

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