Water → N-[4-Chloro-2-(2-methyl-pyridine-3-carbonyl)-phenyl]-2,2-dimethyl-propionamide

HRID 730103Notes

Reaction equation

HRID 730103 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[CH:4][CH:3]=1.[CH2:15]([Li])[CH2:16][CH2:17][CH3:18].[OH2:20]>C1COCC1.CCCCCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:11])([CH3:13])[CH3:12])=[C:6]([C:15]([C:16]2[C:5]([CH3:4])=[N:8][CH:9]=[CH:18][CH:17]=2)=[O:20])[CH:7]=1

Participants

6

Reactant 3

HCID 962WaterHCID 182511Propanamide, N-(4-chlorophenyl)-2,2-dimethyl-HCID 178418339Butyllithium

Product 1

HCID 22327308N-[4-Chloro-2-(2-methyl-pyridine-3-carbonyl)-phenyl]-2,2-dimethyl-propionamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a magnetically stirred solution of N-(4-chloro-phenyl)-2,2-dimethyl-propionamide (3.16 g, 14.9 mmol) in dry THF was added 2.5M n-butyllithium in hexane at −40° C. and the mixture was stirred at 0° C. for 2 h and a suspension of white solid resulted. A solution of the Weinreb amide (1.80 g, 10.0 mmol) in dry THF was added drop wise and the reaction was stirred at ambient temp overnight. The mixture was diluted with water and extracted with ethyl acetate and the organic layer was dried (MgSO4), filtered and concentrated. Chromatography on silica gel (20-30% EtOAc/Hexane) provided the desired N-[4-Chloro-2-(2-methyl-pyridine-3-carbonyl)-phenyl]-2,2-dimethyl-propionamide as a waxy bright yellow solid (2.28 g, 6.89 mmol):

Workup

  1. additiona suspension of white solid
  2. customresulted
  3. stirringthe reaction was stirred at ambient temp overnight
  4. extractionextracted with ethyl acetate
  5. dry with materialthe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-2cff2a2ee6e642e598f1c6fa09035bf6
Source dataset
uspto-grants-2009_09
Patent number
US07582661B2

Reaction notes

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