Hydrochloric Acid → Parecoxib Impurity 67

HRID 29043Notes

Reaction equation

HRID 29043 reaction equation
C([O:4][CH2:5][C:6]1[O:10][N:9]=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:7]=1[C:17]1[CH:22]=[CH:21][C:20]([S:23]([NH:26][C:27](=[O:30])[CH2:28][CH3:29])(=[O:25])=[O:24])=[CH:19][CH:18]=1)CC.[OH-].[Na+].Cl>CO>[OH:4][CH2:5][C:6]1[O:10][N:9]=[C:8]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:7]=1[C:17]1[CH:22]=[CH:21][C:20]([S:23]([NH:26][C:27](=[O:30])[CH2:28][CH3:29])(=[O:24])=[O:25])=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 22643596HCID 22643596, compound

Product 1

HCID 22643548Parecoxib Impurity 67Yield 83%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The N-[[4-(5-propoxymethyl-3-phenylisoxazol-4-yl]phenyl]sulfonyl]propanamide (Step 1) was dissolved in methanol and NaOH solution (0.89 mL of 2.5 N, 2.24 mmol) added with stirring. After 12 hours, the reaction was acidified with 1 N HCl solution and extracted with a mixture of dichloromethane and ethyl acetate. The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo yielding N-[[4-(5-hydroxymethyl-3-phenylisoxazol-4-yl]phenyl]sulfonyl]propanamide (0.238 g, 83%) of sufficient purity to use in the next step.

Workup

  1. extractionextracted with a mixture of dichloromethane and ethyl acetate
  2. dry with materialThe combined organic phases were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c720747df6544ab496bd1c4c04bf7baa
Source dataset
uspto-grants-2008_09
Patent number
US07420061B2

Reaction notes

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