Hydrochloric Acid → 2-CYCLOPROPYLAMINONICOTINIC ACID

HRID 1840628Notes

Reaction equation

HRID 1840628 reaction equation
[OH-:1].[K+].[CH:3]1([NH:6][C:7]2C(C#N)=C[CH:10]=[CH:9][N:8]=2)[CH2:5][CH2:4]1.[CH2:15]([OH:18])[CH2:16][CH3:17].Cl>O>[CH:3]1([NH:6][C:7]2[C:16]([C:15]([OH:1])=[O:18])=[CH:17][CH:10]=[CH:9][N:8]=2)[CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 10311-PropanolHCID 14797Potassium HydroxideHCID 115137932-(cyclopropylamino)nicotinonitrile

Product 1

HCID 100351632-CYCLOPROPYLAMINONICOTINIC ACID

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 45% aqueous KOH solution (187g, 1.5 mol) was charged to a mixture of the product from Example 1 and 300 ml of 1-propanol. The mixture was heated at reflux temperature for about 5 hours whereupon TLC analysis showed complete hydrolysis of the nitrile. The reaction mixture was cooled to ambient temperature and treated with 94 g of water that was needed to remove the 1-propanol by azeotropic distillation. About 330 g of water/1-propanol azeotrope was distilled off at 62° C. and 21.1 in. Hg. Water (130 g) was added to the reaction mixture and the mixture chilled to 5-10° C. Concentrated hydrochloric acid (148 g, 1.5 mol) was added at such a rate that the temperature could be maintained below 30° C. After about 80-90% of the acid was added the zwitterion began to precipitate out, making the mixture quite thick. When all the acid had been added, the solid product was collected by filtration, using 90 ml of cold water to rinse out the reaction vessel onto the filter cake. The product was dried to yield 68.12 g. of the zwitterion.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux temperature for about 5 hours whereupon TLC analysis
  3. customto remove the 1-propanol
  4. distillationby azeotropic distillation
  5. distillationAbout 330 g of water/1-propanol azeotrope was distilled off at 62° C.
  6. additionWater (130 g) was added to the reaction mixture
  7. temperaturethe mixture chilled to 5-10° C
  8. temperaturecould be maintained below 30° C
  9. customto precipitate out
  10. additionWhen all the acid had been added
  11. filtrationthe solid product was collected by filtration
  12. washto rinse out the reaction vessel onto the filter cake
  13. customThe product was dried
  14. customto yield 68.12 g

Sources & evidence

ORD record
ord-49987c69f0b94525978df6f37a241b9d
Source dataset
uspto-grants-2004_01
Patent number
US06680383B1

Reaction notes

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