Water → N-Benzyl-3-(2-hydroxyethyl)pyridine-4-carboxamide

HRID 856913Notes

Reaction equation

HRID 856913 reaction equation
C([Li])CCC.[CH2:6]([NH:13][C:14]([C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1)=[O:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH2:22]1[O:24][CH2:23]1.O>CCCCCC.C1COCC1.O1CCOCC1>[CH2:6]([NH:13][C:14]([C:16]1[CH:21]=[CH:20][N:19]=[CH:18][C:17]=1[CH2:22][CH2:23][OH:24])=[O:15])[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

8

Reactant 4

HCID 962WaterHCID 6354Ethylene OxideHCID 233151n-benzylisonicotinamideHCID 178418339Butyllithium

Product 1

HCID 21865004N-Benzyl-3-(2-hydroxyethyl)pyridine-4-carboxamideYield 24.1%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 312751,4-DioxaneSolvent

Procedure

Butyl lithium (61.5 mL of a 1.6 M solution in hexane, 98.5 mmol) was added dropwise over 10 min to a stirred solution of N-benzyl-4-pyridinecarboxamide (9.94 g, 46.9 mmol) in THF (200 mL) at −78° C. under N2. The reaction mixture immediately turned dark blue, and was stirred for 1 h. A solution of ethylene oxide (2.27 g, 51.6 mmol) in dioxane (10 mL) was then added and the resulting mixture stirred at −78° C. for 3 h, after which time it was warmed to room temperature and quenched with MeOH (40 mL). The quenched reaction mixture was poured into H2O (200 mL) and extracted with EtOAc (3×150 mL). The combined organic extracts were washed with brine (150 mL), dried (MgSO4) and concentrated under reduced pressure. The crude material was purified by column chromatography on silica using 5–10% MeOH in DCM as the eluent to yield the desired alcohol (2.9 g, 24%). MS (ES+) 257 (M+1).

Workup

  1. stirringthe resulting mixture stirred at −78° C. for 3 h
  2. customquenched with MeOH (40 mL)
  3. customThe quenched reaction mixture
  4. extractionextracted with EtOAc (3×150 mL)
  5. washThe combined organic extracts were washed with brine (150 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by column chromatography on silica using 5–10% MeOH in DCM as the eluent

Sources & evidence

ORD record
ord-f0c63b48aa3c438fbcbdd391737691be
Source dataset
uspto-grants-2006_12
Patent number
US07144887B2

Reaction notes

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