Benzyl Alcohol → 2-Chloro-6-benzyloxypyridine-4-carboxylic acid

HRID 1096954Notes

Reaction equation

HRID 1096954 reaction equation
[CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[Cl:11][C:12]1[CH:17]=[C:16]([C:18]([OH:20])=[O:19])[CH:15]=[C:14](Cl)[N:13]=1.Cl>CN(C=O)C>[Cl:11][C:12]1[CH:17]=[C:16]([C:18]([OH:20])=[O:19])[CH:15]=[C:14]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[N:13]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 948302,6-Dichloroisonicotinic acid

Product 1

HCID 27625082-Chloro-6-benzyloxypyridine-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

With cooling with ice, benzyl alcohol (3.4 mL) was dropwise added to a DMF (100 mL) suspension of sodium hydride (3.2 g). This was stirred at that temperature for 1 hour, then a DMF (30 mL) solution of 2,6-dichloropyridine-4-carboxylic acid (6.38 g) was dropwise added to the reaction solution with cooling with ice, and stirred at that temperature for 1 hour and 30 minutes and then overnight at 90° C. With cooling with ice, diluted hydrochloric acid was added to it, and extracted with ethyl acetate. The organic layer was washed with saturated saline water, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. A mixed solution of hexane/ethyl acetate=2/1 was added to the residue, and the formed precipitate was removed. The filtrate was concentrated under reduced pressure to obtain the title compound as a yellow oil. Not purified, this was used in the next step.

Workup

  1. temperaturewith cooling with ice
  2. stirringstirred at that temperature for 1 hour and 30 minutes
  3. customovernight
  4. customat 90° C
  5. additionwas added to it
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with saturated saline water
  8. dry with materialdried with anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. additionA mixed solution of hexane/ethyl acetate=2/1 was added to the residue
  12. customthe formed precipitate was removed
  13. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-b172f326bf384407922bb430d8e04a3a
Source dataset
uspto-grants-2012_03
Patent number
US08138197B2

Reaction notes

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