Pyridine-2-carbonitrile → HCID 21264597, compound

HRID 567120Notes

Reaction equation

HRID 567120 reaction equation
[CH3:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1Br.[Mg].BrBr.[C:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1)#N.[Cl-].[NH4+].[O:30]1CCCC1>O>[CH3:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1)=[O:30]

Participants

8

Reactant 6

HCID 7522Pyridine-2-carbonitrileHCID 8028Tetrahydrofuran3×HCID 24408Bromine2×HCID 25517Ammonium ChlorideHCID 2235521-bromo-2-[(2-methylphenoxy)methyl]benzeneHCID 5462224Magnesium

Product 1

HCID 21264597HCID 21264597, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
-20 °C

Procedure

10 g (0.036 mol) of 2-[(2-methylphenoxy)-methyl]-1-bromo-benzene (EP-A 525 516, page 113) are dissolved in 40 ml of tetrahydrofuran. 3 g of this solution are added to 0.88 g (0.036 mol) of magnesium turnings. After the addition of a drop of bromine, the mixture is heated. Once the reaction has set in, the remainder of the bromine compound dissolved in tetrahydrofuran is added and the mixture is heated under reflux for one hour. At −20° C., 3.76 g (0.036 mol) of 2-cyanopyridine dissolved in 10 ml of tetrahydrofuran are then added to the reaction mixture, and the mixture is stirred at −20° C. for 1 hour. A solution of 10 g of ammonium chloride in 100 ml of water is added and the crude intermediate (the ketimine of the end product) is extracted with diethyl ether. The solution is concentrated and the residue is admixed with a mixture of 15 ml of 36% strength aqueous hydrochloric acid, 50 ml of water and 100 ml of dimethylformamide. The mixture is stirred at 25° C. for one hour and ice is then added to the mixture which is made alkaline with 50% strength aqueous sodium hydroxide solution and extracted with diethyl ether. The organic phase is dried over sodium sulphate and concentrated under reduced pressure. The residue is chromatographed over silica gel using diethyl ether/petroleum ether (1:1). 3.94 g (36% of theory) of 2-[2-(2-methylphenoxymethyl)-benzoyl]-pyridine are obtained.

Workup

  1. temperaturethe mixture is heated
  2. additionis added
  3. temperaturethe mixture is heated
  4. temperatureunder reflux for one hour
  5. additionare then added to the reaction mixture
  6. extractionthe crude intermediate (the ketimine of the end product) is extracted with diethyl ether
  7. concentrationThe solution is concentrated
  8. additionthe residue is admixed with a mixture of 15 ml of 36% strength aqueous hydrochloric acid, 50 ml of water and 100 ml of dimethylformamide
  9. stirringThe mixture is stirred at 25° C. for one hour
  10. additionice is then added to the mixture which
  11. extractionextracted with diethyl ether
  12. dry with materialThe organic phase is dried over sodium sulphate
  13. concentrationconcentrated under reduced pressure
  14. customThe residue is chromatographed over silica gel

Sources & evidence

ORD record
ord-b042f4c5e02348708a60922cd41c3d6d
Source dataset
uspto-grants-2001_01
Patent number
US06177459B1

Reaction notes

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