Valdecoxib IMpurity F Chemical Properties

Melting point:

108-109°C

Boiling point:

440.6±45.0 °C(Predicted)

Density 

1.340±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

solubility 

Benzene (Slightly), DMSO (Slightly)

form 

Solid

pka

-3.74±0.50(Predicted)

color 

White to Off-White

Stability:

Hygroscopic

InChI

InChI=1S/C16H12ClNO3S/c1-11-15(12-7-9-14(10-8-12)22(17,19)20)16(18-21-11)13-5-3-2-4-6-13/h2-10H,1H3

InChIKey

NVKQPOHDVWNXRP-UHFFFAOYSA-N

SMILES

C1(S(Cl)(=O)=O)=CC=C(C2=C(C)ON=C2C2=CC=CC=C2)C=C1

Valdecoxib IMpurity F Usage And Synthesis

Uses

Valdecoxib Sulfonyl Chloride is an impurity in the preparation of the cyclooxygenase-2 inhibitor, Valdecoxib (V090000) and its metabolites.

Synthesis

General procedure for the synthesis of 4-(5-methyl-3-phenyl-4-isoxazolyl)benzenesulfonyl chloride from 5-methyl-3,4-diphenyl-isoxazole: Dichloromethane was added to the reactor and cooled to 10-15 °C, and 98.00 kg of chlorosulfonic acid was slowly added. 3,4-Diphenyl-5-methylisoxazole was dissolved in 50 liters of dichloromethane and slowly added to the reaction material at 0-10°C, followed by heating and refluxing for 9-11 hours. Upon completion of the reaction, the reaction material was cooled to 25-35°C. The reaction material was slowly added to 175 liters of cold water at 0-10°C and the temperature was raised to 25-35°C. The aqueous and organic layers were separated and the aqueous layer was extracted with 125 liters of dichloromethane in two batches. The organic layer was combined and washed three times with 575 liters of water. The combined organic layers were added to a reactor and the dichloromethane was removed by distillation below 60°C. The crude solid obtained was dissolved in 250 liters of cyclohexane and heated to reflux for 30-45 minutes. Subsequently, water was added to the reaction material and heated to reflux again for 15-30 minutes, and the organic layer and the underlying aqueous layer were separated after the reaction material settled. The organic layer was cooled to 25-35°C, maintained at this temperature for 45-60 minutes and then filtered and washed with cyclohexane. This washing process was repeated twice. Finally, the wet compound was dried at 50-55°C to give 4-(5-methyl-3-phenyl-4-isoxazole)benzenesulfonyl chloride (yield 21.3 kg, 59.15%).

References

[1] Synthetic Communications, 2012, vol. 42, # 5, p. 639 - 649
[2] Patent: EP1550658, 2005, A1. Location in patent: Page/Page column 7
[3] Patent: WO2005/123701, 2005, A1. Location in patent: Page/Page column 38-39
[4] Patent: US2003/105334, 2003, A1
[5] Patent: CN105367508, 2016, A. Location in patent: Paragraph 0038; 0045

Valdecoxib IMpurity F(509074-26-4)Related Product Information

• N-((4-(5-Methyl-3-phenylisoxazol-4-yl)phenyl)sulfonyl)acetaMide
• Parecoxib Impurity H
• Acotiamide Impurity
• BenzenesulfonaMide, 3-[4-[4-(aMinosulfonyl)phenyl]-5-Methyl-3-isoxazolyl]-
• Valdecoxib IMpurity B
• 5-METHYL-3,4-DIPHENYL-4,5-DIHYDROISOXAZOL-5-OL
• N-((4-(5-Methyl-3-phenylisoxazol-4-yl)phenyl)sulfonyl)isobutyraMide
• Valdecoxib IMpurity D
• 4-[(5-Methyl-3-phenyl-4-isoxazolyl)methyl]benzenesulfonamide
• Valdecoxib 3'-Sulfonyl Chloride IMpurity
• Parecoxib
• Valdecoxib IMpurity-E
• 5-Methyl-3-phenyl-4-(phenylMethyl)isoxazole
• Deoxybenzoin Oxime
• 1-Hydroxy Valdecoxib