Sodium Hydroxide → Pantoprazole

HRID 2245622Notes

Reaction equation

HRID 2245622 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-].[Na+].ClN1C(=[O:34])C2=CC=CC=C2C1=O.S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+]>CN(C)C=O.C(O)(=O)C.C(#N)C>[CH3:22][O:21][C:17]1[CH:16]=[CH:15][N:14]=[C:13]([CH2:12][S+:11]([O-:34])[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

8

Reactant 4

HCID 14798Sodium HydroxideHCID 18997N-ChlorophthalimideHCID 656671Sodium PyrosulfiteHCID 9799341Pantoprazole sulfide

Product 1

HCID 178493214PantoprazoleYield 98.3%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
-10 °C

Procedure

A flask equipped with a stirrer is charged with acetonitrile (40 ml). Under mixing, compound VI (5 g) is added followed by 2N NaOH (17.5 ml, 4.9 eq.). The flask is cooled to −10° C. A solution of N-chlorophthalimide (2.6 g, 1.1 eq.) in dimethylformamide (DMF) (10 ml) is added dropwise over 45 min. The two-phase mixture is stirred at room temperature over 1 h. Saturated aqueous Na2S2O5 (20 ml) is then added, and the pH is adjusted to 8.5 with acetic acid. The phases are separated. The organic phase is washed with brine, and the aqueous phase is extracted twice with ethyl acetate. The organic phases are combined, dried, and evaporated to dryness. The residue is taken up in a mixture of ethyl acetate (10 ml), toluene (10 ml), and hexane (30 ml). On standing, a precipitate forms in the solution which is separated by filtration to give pantoprazole (5.13 g, 98%) containing 0.3% compound VI and free of sulfone within the limit of UV detection.

Workup

  1. customA flask equipped with a stirrer
  2. additionUnder mixing
  3. customThe phases are separated
  4. washThe organic phase is washed with brine
  5. extractionthe aqueous phase is extracted twice with ethyl acetate
  6. customdried
  7. customevaporated to dryness
  8. additionThe residue is taken up in a mixture of ethyl acetate (10 ml), toluene (10 ml), and hexane (30 ml)
  9. customa precipitate forms in the solution which is separated by filtration

Sources & evidence

ORD record
ord-806da759e4f5414ba0785caa857e1a68
Source dataset
uspto-grants-2010_03
Patent number
US07683177B2

Reaction notes

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