Sodium Chloride → Rabeprazole

HRID 428640Notes

Reaction equation

HRID 428640 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-].[Na+].ClN1C(=[O:33])CCC1=O.S([O-])([O-])(=O)=S.[Na+].[Na+].C([O-])(=O)C.[NH4+].[Cl-].[Na+]>CN(C)C=O.O.C(OCC)(=O)C>[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:33])[C:8]=1[CH3:24]

Participants

10

Reactant 6

HCID 5234Sodium ChlorideHCID 14798Sodium HydroxideHCID 24477Sodium ThiosulfateHCID 31398ChlorosuccinimideHCID 517165Ammonium AcetateHCID 9949996Rabeprazole-thioether

Product 1

HCID 5029RabeprazoleYield 90.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

2-{[4-(3-Methoxypropoxy)-3-methylpyridin-2-yl]methylthio}-1H-benzimidazole (5.0 g 14.6 mmol; referred to as Compound I hereinafter) was dissolved in 20 ml of N,N-dimethylformamide, followed by the addition of a 2N aqueous solution of sodium hydroxide (18 ml). A solution (10 ml) of N-chlorosuccinimide (2.71 g, 20.3 mmol) in N,N-dimethylformamide was added dropwise to the solution at −20° C. to −10° C. The reaction mixture was reacted at −15° C. to −7° C. for 1.5 hr. To the reaction mixture was added a 10% aqueous solution of sodium thiosulfate (5 ml), stirred for 2 min and then, a solution (60 ml) of ammonium acetate (23.1 g) in water was added thereto. 60 ml of ethyl acetate and 10 g of sodium chloride were added thereto to extract the reaction mixture, and the aqueous layer was further extracted with ethyl acetate (40 ml). The organic layers were combined, washed with a 15% aqueous solution of sodium chloride (80 ml) for three times and then, the solvent was evaporated. To the resulting oil was added 12 ml of ethyl acetate, 28 ml of hexane and 10 ml of toluene, followed by stirring at room temperature for 1 hr. The resulting crystals were collected by filtration, washed with a solvent mixture (10 ml) of 30% ethyl acetate and hexane for two times and then, dried under reduced pressure, to give the title compound (4.7 g, yield; 90.6%) as grayish white crystals.

Workup

  1. customThe reaction mixture was reacted at −15° C. to −7° C. for 1.5 hr
  2. extractionto extract the reaction mixture
  3. extractionthe aqueous layer was further extracted with ethyl acetate (40 ml)
  4. washwashed with a 15% aqueous solution of sodium chloride (80 ml) for three times
  5. customthe solvent was evaporated
  6. additionTo the resulting oil was added 12 ml of ethyl acetate, 28 ml of hexane and 10 ml of toluene
  7. stirringby stirring at room temperature for 1 hr
  8. filtrationThe resulting crystals were collected by filtration
  9. washwashed with a solvent mixture (10 ml) of 30% ethyl acetate and hexane for two times
  10. customdried under reduced pressure

Sources & evidence

ORD record
ord-0fd77b51ed9e421ca906e406fc73e268
Source dataset
uspto-grants-2001_11
Patent number
US06313303B1

Reaction notes

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