1-Bromo-3-chloropropane → 5-(3-Chloropropoxy)-2-pyridine-carboxylic acid methyl ester

HRID 1395192Notes

Reaction equation

HRID 1395192 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][N:6]=1)=[O:4].[H-].[Na+].Br[CH2:15][CH2:16][CH2:17][Cl:18]>CN(C)C=O>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:15][CH2:16][CH2:17][Cl:18])=[CH:7][N:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 80061-Bromo-3-chloropropaneHCID 24758Sodium hydrideHCID 4715126Methyl 5-hydroxypyridine-2-carboxylate

Product 1

HCID 537524315-(3-Chloropropoxy)-2-pyridine-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

The solution of 13.8 g of 5-hydroxy-2-pyridinecarboxylic acid methyl ester in 200 ml of dimethylformamide is added over a period of 45 minutes to a suspension of 4.3 g of sodium hydride in (57% mineral oil dispersion) 50 ml of dimethylformamide with stirring at room temperature. The mixture is stirred at room temperature for one hour and then is cooled to 5°-10°. To this cooled mixture is added a solution of 19.3 g of 1-bromo-3-chloropropane in 100 ml of dimethylformamide. The mixture is heated to 45°-50° and stirred at 45°-50° for 4 hours and 30 minutes. After that, the mixture is cooled, filtered and the filtrate evaporated to a residue. The residue is partitioned between methylene chloride and water and the layers are separated. The methylene chloride layer is washed with water and dried over anhydrous sodium sulfate. The methylene chloride solution is filtered and the filtrate evaporated to yield 5-(3-chloropropoxy)-2 -pyridinecarboxylic acid methyl ester.

Workup

  1. stirringThe mixture is stirred at room temperature for one hour
  2. temperatureis cooled to 5°-10°
  3. temperatureThe mixture is heated to 45°-50°
  4. stirringstirred at 45°-50° for 4 hours and 30 minutes
  5. temperatureAfter that, the mixture is cooled
  6. filtrationfiltered
  7. customthe filtrate evaporated to a residue
  8. customThe residue is partitioned between methylene chloride and water
  9. customthe layers are separated
  10. washThe methylene chloride layer is washed with water
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationThe methylene chloride solution is filtered
  13. customthe filtrate evaporated

Sources & evidence

ORD record
ord-9cf858ca54d9471fab7ef703c01584c6
Source dataset
uspto-grants-1980_05
Patent number
US04202901

Reaction notes

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