Hydrochloric Acid → Carfentrazone

HRID 1851703Notes

Reaction equation

HRID 1851703 reaction equation
N[C:2]1[C:3]([Cl:19])=[CH:4][C:5]([F:18])=[C:6]([N:8]2[C:12](=[O:13])[N:11]([CH:14]([F:16])[F:15])[C:10]([CH3:17])=[N:9]2)[CH:7]=1.[ClH:20].[C:21]([OH:25])(=[O:24])[CH:22]=[CH2:23].[Cl-].[Li+].N([O-])=O.[Na+]>CC(C)=O>[Cl:20][CH:22]([CH2:23][C:2]1[CH:7]=[C:6]([N:8]2[C:12](=[O:13])[N:11]([CH:14]([F:16])[F:15])[C:10]([CH3:17])=[N:9]2)[C:5]([F:18])=[CH:4][C:3]=1[Cl:19])[C:21]([OH:25])=[O:24]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6581Acrylic AcidHCID 433294Lithium ChlorideHCID 10880883AGN-PC-0NC5KNHCID 23668193Sodium Nitrite

Product 1

HCID 443229CarfentrazoneYield 83.5%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a reaction flask was added a mixture of 156 g of 1-(5-amino-4-chloro-2-fluorophenyl)-4-difluoromethyl-3-methyl-1H-1,2,4-triazol-5-one and 500 g of acetone. The mixture was stirred and dissolved, and then 45 g of hydrogen chloride was introduced while maintaining a temperature between 0˜5° C. 780 g of acrylic acid, 6 g of cuprous chloride and 16 g of lithium chloride were successively added. Then 95 g of a 45% aqueous solution of sodium nitrite was added dropwise below a liquid level. After the adding was completed, the mixture was stirred for additional 0.5 hour. The reaction mixture was concentrated under reduced pressure. The residue was diluted with 1000 ml of methyl benzene, washed with 300 ml of water and twice with 300 ml of a 5% diluted hydrochloride acid and then with 400 ml of water, and then concentrated under reduced pressure. After cooling, crystallized products were collected by filtration and dried, to give 171 g of 2-chloro-3-{2-chloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorophenyl}propionic acid as white solids with a purity of 98.1%.

Workup

  1. additionTo a reaction flask was added
  2. dissolutiondissolved
  3. temperaturewhile maintaining a temperature between 0˜5° C
  4. stirringthe mixture was stirred for additional 0.5 hour
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. additionThe residue was diluted with 1000 ml of methyl benzene
  7. washwashed with 300 ml of water and twice with 300 ml of a 5% diluted hydrochloride acid
  8. concentrationwith 400 ml of water, and then concentrated under reduced pressure
  9. temperatureAfter cooling
  10. customcrystallized products
  11. filtrationwere collected by filtration
  12. customdried

Sources & evidence

ORD record
ord-480a3f742bf248b3aea9b43b66161f2d
Source dataset
uspto-grants-2015_02
Patent number
US08957220B2

Reaction notes

Loading…