Sodium Hydroxide → Rabeprazole-thioether

HRID 556003Notes

Reaction equation

HRID 556003 reaction equation
Cl[CH2:2][C:3]1[C:8]([CH3:9])=[C:7]([O:10][CH2:11][CH2:12][CH2:13][O:14][CH3:15])[CH:6]=[CH:5][N:4]=1.[N:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[NH:18][C:17]=1[SH:25].[OH-].[Na+]>C(O)C>[CH3:15][O:14][CH2:13][CH2:12][CH2:11][O:10][C:7]1[CH:6]=[CH:5][N:4]=[C:3]([CH2:2][S:25][C:17]2[NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[N:16]=2)[C:8]=1[CH3:9]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 110316672-(Chloromethyl)-4-(3-methoxypropoxy)-3-methylpyridineHCID 178527775HCID 178527775, compound

Product 1

HCID 9949996Rabeprazole-thioetherYield 101%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2-Chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine (53.2 g (200 mmol)), denatured ethanol (320 ml), 2-benzimidazole thiol (30.2 g (201 mmol)) and sodium hydroxide (26.8 g (670 mmol)) were added together and reacted for about 2 hours at 50° C. After disappearance of the raw materials had been confirmed by TLC, this solution was concentrated under a reduced pressure and ethyl acetate (430 ml) and water (340 ml) were added thereto, followed by stirring and standing, and the water layer was then separated. The organic layer was washed with 10% aqueous sodium hydroxide solution (110 ml) and water (2×110 ml) and concentrated under a reduced pressure to obtain crude 2-[{4-(3-methoxypropoxy)-3-methylpyridin-2-yl}methylthio]-1H-benzimidazole (69.0 g) (HPLC purity 98.7%, yield 101%).

Workup

  1. customreacted for about 2 hours at 50° C
  2. concentrationthis solution was concentrated under a reduced pressure and ethyl acetate (430 ml) and water (340 ml)
  3. additionwere added
  4. customthe water layer was then separated
  5. washThe organic layer was washed with 10% aqueous sodium hydroxide solution (110 ml) and water (2×110 ml)
  6. concentrationconcentrated under a reduced pressure

Sources & evidence

ORD record
ord-6fe93b4c0a374189a15c2a941c0361f7
Source dataset
uspto-grants-2011_11
Patent number
US08053580B2

Reaction notes

Loading…