Carbon Dioxide → 3-(((Tert-butoxy)carbonyl)amino)pyridine-4-carboxylic acid

HRID 1913701Notes

Reaction equation

HRID 1913701 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[C:20](=[O:22])=[O:21]>CCCCCC.O1CCCC1.O>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][C:14]=1[C:20]([OH:22])=[O:21])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 280Carbon DioxideHCID 109323213-(Boc-amino)pyridineHCID 178418339Butyllithium

Product 1

HCID 212015233-(((Tert-butoxy)carbonyl)amino)pyridine-4-carboxylic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent2×

Procedure

While a mixture of 1.16 g of 3-(tert-butoxycarbonylamino)pyridine and 25 ml of tetrahydrofuran was cooled in a dry ice-acetone bath, 8.5 ml of 1.65 M hexane solution of n-butyllithium was added so that the temperature of the reaction mixture did not exceed −60° C. The reaction mixture was stirred for 15 minutes. Cooling was stopped. Then, the reaction mixture was stirred until the temperature became 0° C. The reaction mixture was cooled in a dry ice-acetone bath again. After injection of carbon dioxide, cooling was stopped, and the reaction mixture was stirred at room temperature for two hours. After water was added, most of tetrahydrofuran and hexane was removed by concentration under reduced pressure. The residue was ice-cooled and 3N hydrochloric acid was added so as to adjust pH to about 3. Extraction with a mixture solvent (4:1) of ethyl acetate to tetrahydrofuran was carried out several times. The combined organic layers were washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 0.53 g of 3-(tert-butoxycarbonyl amino)isonicotinic acid.

Workup

  1. temperaturewas cooled in a dry ice-acetone bath
  2. customdid not exceed −60° C
  3. temperatureCooling
  4. stirringThen, the reaction mixture was stirred until the temperature
  5. custombecame 0° C
  6. temperatureThe reaction mixture was cooled in a dry ice-acetone bath again
  7. stirringthe reaction mixture was stirred at room temperature for two hours
  8. customwas removed by concentration under reduced pressure
  9. temperaturecooled
  10. addition3N hydrochloric acid was added so as
  11. extractionExtraction with a mixture solvent (4:1) of ethyl acetate to tetrahydrofuran
  12. washThe combined organic layers were washed with a saturated sodium chloride solution
  13. dry with materialdried over anhydrous sodium sulfate
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-60f58011f3f44dbbb568f3cd6ba3a7e4
Source dataset
uspto-grants-2013_12
Patent number
US08609705B2

Reaction notes

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