Sodium Hydroxide → Pantoprazole

HRID 2245617Notes

Reaction equation

HRID 2245617 reaction equation
[F:1][CH:2]([F:25])[O:3][C:4]1[CH:24]=[CH:23][C:7]2[NH:8][C:9]([S:11][CH2:12][C:13]3[C:18]([O:19][CH3:20])=[C:17]([O:21][CH3:22])[CH:16]=[CH:15][N:14]=3)=[N:10][C:6]=2[CH:5]=1.[OH-:26].[Na+].[O-]Cl.[Na+]>C(OCC)(=O)C>[CH3:22][O:21][C:17]1[CH:16]=[CH:15][N:14]=[C:13]([CH2:12][S+:11]([O-:26])[C:9]2[NH:8][C:7]3[CH:23]=[CH:24][C:4]([O:3][CH:2]([F:1])[F:25])=[CH:5][C:6]=3[N:10]=2)[C:18]=1[O:19][CH3:20]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 9799341Pantoprazole sulfideHCID 23665760Sodium Hypochlorite

Product 1

HCID 178493214PantoprazoleYield 71%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

A flask equipped with a stirrer is charged with ethyl acetate (140 ml). Under mixing, 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl) methyl]thio]-1H-benzimidazole VI (5 g, 13.6 mmol) is added to the flask followed by 18.8% aq. NaOH (11.5 ml, d=1.16 g ml−1, 4.9 eq.). The reactor is cooled to −10° C. 9.7% NaOCl (9.7 ml, d=1.16 g ml−1, 1.04 eq.) is added dropwise over 15 min. The two-phase mixture is stirred at room temperature for 3 h. The phases are then separated, and 27% aq. sodium metabisulfite (Na2S2O5) (7 ml) is added to the aqueous phase to quench unreacted oxidant. The organic phase is washed with water, and the aqueous phase is washed twice with ethyl acetate. The organic phases are combined, dried over sodium sulfate (Na2SO4), and evaporated under 20 mm Hg vacuum. The resulting oil is triturated with methyl t-butyl ether and filtered to obtain pantoprazole (3.7 g, yield 71%) which contains 0.04% sulfone and 0.03% compound VI as within the limit of UV detection.

Workup

  1. customA flask equipped with a stirrer
  2. additionUnder mixing
  3. customThe phases are then separated
  4. addition27% aq. sodium metabisulfite (Na2S2O5) (7 ml) is added to the aqueous phase
  5. customto quench unreacted oxidant
  6. washThe organic phase is washed with water
  7. washthe aqueous phase is washed twice with ethyl acetate
  8. dry with materialdried over sodium sulfate (Na2SO4)
  9. customevaporated under 20 mm Hg vacuum
  10. customThe resulting oil is triturated with methyl t-butyl ether
  11. filtrationfiltered

Sources & evidence

ORD record
ord-68f1ddca1db3473080c5a37a964ee648
Source dataset
uspto-grants-2010_03
Patent number
US07683177B2

Reaction notes

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