Water → Rabeprazole

HRID 556014Notes

Reaction equation

HRID 556014 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([CH2:13][S:14][C:15]2[NH:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[N:16]=2)[C:8]=1[CH3:24].[OH-:25].[Na+].O>ClCCl>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([CH2:13][S:14]([C:15]2[NH:16][C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[N:19]=2)=[O:25])[C:8]=1[CH3:24]

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 9949996Rabeprazole-thioether

Product 1

HCID 5029RabeprazoleYield 55.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-[{4-(3-Methoxypropoxy)-3-methylpyridin-2-yl}methylthio]-1H-benzimidazole (25.0 g (72.8 mmol)) was dissolved in dichloromethane and cooled. Then, mcpba (70.2% purity; 10.7 g (43.7 mmol)) was added gradually so that the internal temperature did not exceed −15° C. 10% Aqueous sodium hydroxide solution (70.8 ml) was then added, and after stirring and still standing the water layer was separated. The separated water layer was washed with dichloromethane (48 ml) twice. After addition of a 2N-ammonium acetate aqueous solution, the water layer was extracted with dichloromethane (48 ml) twice. The dichloromethane layer was washed with water (48 ml) twice, concentrated under a reduced pressure, crystallized with dichloromethane (27 ml) and ether (220 ml), and filtered to obtain 2-[{4-(3-methoxypropoxy)-3-methylpyridin-2-yl}methylsulfinyl]-1H-benzimidazole (14.5 g) (HPLC purity 99.1%, yield 55.4%).

Workup

  1. temperaturecooled
  2. additionThen, mcpba (70.2% purity; 10.7 g (43.7 mmol)) was added gradually so that the internal temperature
  3. customdid not exceed −15° C
  4. customwas separated
  5. washThe separated water layer was washed with dichloromethane (48 ml) twice
  6. additionAfter addition of a 2N-ammonium acetate aqueous solution
  7. extractionthe water layer was extracted with dichloromethane (48 ml) twice
  8. washThe dichloromethane layer was washed with water (48 ml) twice
  9. concentrationconcentrated under a reduced pressure
  10. customcrystallized with dichloromethane (27 ml) and ether (220 ml)
  11. filtrationfiltered

Sources & evidence

ORD record
ord-a12ff949a07c4995aca3ac1e43919707
Source dataset
uspto-grants-2011_11
Patent number
US08053580B2

Reaction notes

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