Tetrahydrofuran → 5-(4-Chlorophenoxy)-2-(3,4-dimethoxybenzoyl)pyridine

HRID 1031502

Reaction equation

HRID 1031502 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:10][CH3:11])[C:5]([O:8][CH3:9])=[CH:6][CH:7]=1.CCCCCC.C([Li])CCC.[Cl:23][C:24]1[CH:38]=[CH:37][C:27]([O:28][C:29]2[CH:30]=[CH:31][C:32]([C:35]#N)=[N:33][CH:34]=2)=[CH:26][CH:25]=1.[O:39]1CCCC1>O.CO>[Cl:23][C:24]1[CH:38]=[CH:37][C:27]([O:28][C:29]2[CH:30]=[CH:31][C:32]([C:35](=[O:39])[C:2]3[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([O:10][CH3:11])[CH:3]=3)=[N:33][CH:34]=2)=[CH:26][CH:25]=1

Participants

8

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 8058HexaneHCID 76114Benzene, 4-bromo-1,2-dimethoxy-HCID 148232325-(4-Chlorophenoxy)picolinonitrileHCID 178418339Butyllithium

Product 1

HCID 148232335-(4-Chlorophenoxy)-2-(3,4-dimethoxybenzoyl)pyridine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

In anhydrous tetrahydrofuran (6 ml) was dissolved 4-bromoveratrol (700 mg). To the solution was added dropwise a 15% n-hexane solution of n-butyllithium (2.2 ml), while stirring under cooling at temperatures ranging from -60° C. to -70° C. under an atmosphere of nitrogen gas. The mixture was stirred at the same temperature range for 20 minutes, and there was added dropwise at temperatures of -70° C. or below a solution of 5-(4-chlorophenoxy)-2-cyanopyridine (500 mg) in dry tetrahydrofuran (6 ml). The mixture was stirred at the same temperature for 30 minutes, and there was added methanol (1 ml) (the temperature rose up to -65° C. from -73° C.), then the temperature of the mixture was slowly warmed to room temperature. To the reaction mixture was added silica gel (3 g), and there was then added water (0.5 ml), and the mixture was stirred at room temperature for 2 hours, and left standing overnight. Silica gel was filtered off, and the filtrate was concentrated. The concentrate was purified by means of a silica gel column chromatography [eluted with a mixture solvent of dichloromethane and ethyl acetate (10:1)] to obtain 5-(4-chloro-phenoxy)-2-(3,4-dimethoxybenzoyl)pyridine (240 mg) as colorless crystals, m.p. 145 to 147° C.

Workup

  1. temperatureunder cooling at temperatures
  2. customranging from -60° C. to -70° C. under an atmosphere of nitrogen gas
  3. stirringThe mixture was stirred at the same temperature range for 20 minutes
  4. stirringThe mixture was stirred at the same temperature for 30 minutes
  5. customrose up to -65° C. from -73° C.
  6. additionTo the reaction mixture was added silica gel (3 g), and there
  7. waitleft
  8. filtrationSilica gel was filtered off
  9. concentrationthe filtrate was concentrated
  10. customThe concentrate was purified by means of a silica gel column chromatography [
  11. washeluted with a mixture solvent of dichloromethane and ethyl acetate (10:1)]

Sources & evidence

ORD record
ord-ced84d71e550470bb84d76514435bd48
Source dataset
uspto-grants-1990_09
Patent number
US04954497

Linked notes

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