Table 3.
Effect of sont on Impurity E (1) content in the formation of PAN (6) from pantoprazole sulfoxide (5).a
| Entry | Parameters | Solvent |
As per PAN Ph. Eur. monograph [15] | |||
|---|---|---|---|---|---|---|
| ACN | DCM | EtOAc | Acetone | |||
| 1 | Appearance | Almost white | Off-white | Off-white | Almost white | White or almost white powder |
| 2 | Water content (%, w/w by KF) | 6.72 | 6.9 | 6.71 | 7.38 | Between 5.9 and 6.9 |
| 3 | Assay by potentiometry (%, w/w) | 100.45 | 100.55 | 99.99 | 90.43 | NLT 99 and NMT 101 |
| 4 | Purity by HPLC | |||||
| a) Pantoprazole 6 | 99.92 | 99.63 | 99.85 | 99.79 | NLT 99.5 | |
| b) Imp A (7) | 0.03 | 0.02 | 0.02 | 0.08 | NMT 0.2 | |
| c) Imp B (4) | 0.02 | 0.01 | nd | nd | NMT 0.1 | |
| d) Imp C (3) | nd | nd | 0.01 | nd | NMT 0.1 | |
| e) Imp D+F (8,9) | nd | 0.02 | nd | nd | NMT 0.2 | |
| f) Imp E (1) | 0.03 | 0.14 | 0.03 | 0.10 | NMT 0.1 | |
| 5 | Yield (%) | 84 | 83 | 77 | 82 | NMT 99.0 |
nd : not detected.
NLT : Not less than.
NMT : Not more than.
a
Reaction conditions: 5-(difluoromethoxy)-1H-benzimidazole-2-th (3), 10 mmol; NaOH, 10 mmol; water, 0.43 mL; solvent, 10 mL at temp 0–5 °C and 20–25 °C for 4–5 h.