Water → Benzimidazole

HRID 507814Notes

Reaction equation

HRID 507814 reaction equation
CO[C:3]1[CH:24]=[CH:23][C:6]2[NH:7][C:8](S(CC3C(C)=C(OC)C(C)=CN=3)=O)=[N:9][C:5]=2[CH:4]=1.C(N(CC)CC)C.ClC(OCC1C=CC=CC=1)=O.O>ClCCl>[NH:7]1[C:6]2[CH:23]=[CH:24][CH:3]=[CH:4][C:5]=2[N:9]=[CH:8]1

Participants

6

Reactant 4

HCID 962WaterHCID 4594OmeprazoleHCID 8471TriethylamineHCID 10387Benzyl chloroformate

Product 1

HCID 5798BenzimidazoleYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

The sulfoxide solution was treated with triethylamine (25.4 mL). The mixture was cooled to 0-10° C. and 95% benzyl chloroformate (13.5 g) in dichloromethane (30 mL) was added while keeping the temperature below 10° C. After stirring for 2-3 hours, water (90 mL) was added. The phases were separated and the aqueous phase was extracted with dichloromethane (60 mL). The combined organic phases were washed with brine (60 mL) and saturated sodium bicarbonate (30 mL) and vacuum distilled to 90 mL. Ethyl acetate (180 mL) was added to the solution and vacuumed distilled to 90 mL. The solution was stirred while 150 mL of heptanes was added at 20-25° C. The suspension was cooled to 0-5° C. and maintained at this temperature for 2-3 hours. The suspension was filtered and the damp cake was pulped in ethyl acetate (30 mL) and heptanes (120 mL) for 1-2 hours. The suspension was filtered, washed with heptanes/ethyl acetate (4/1) (2×30 mL) and dried under vacuum at room temperature to afford 5/6-methoxy-1-benzyloxycarbonyl-2-[[4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole. Weight: 25.91 g. Yield: 59%. Ratio of 5- and 6-methoxy products: 3:2. The analytical data was consistent with the assigned structure.

Workup

  1. customthe temperature below 10° C
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with dichloromethane (60 mL)
  4. washThe combined organic phases were washed with brine (60 mL) and saturated sodium bicarbonate (30 mL) and vacuum
  5. distillationdistilled to 90 mL
  6. additionEthyl acetate (180 mL) was added to the solution
  7. distillationvacuumed distilled to 90 mL
  8. stirringThe solution was stirred while 150 mL of heptanes
  9. additionwas added at 20-25° C
  10. temperatureThe suspension was cooled to 0-5° C.
  11. temperaturemaintained at this temperature for 2-3 hours
  12. filtrationThe suspension was filtered
  13. waitheptanes (120 mL) for 1-2 hours
  14. filtrationThe suspension was filtered
  15. washwashed with heptanes/ethyl acetate (4/1) (2×30 mL)
  16. customdried under vacuum at room temperature

Sources & evidence

ORD record
ord-96ad1ddabebe4267a4f7f9bf1e814e82
Source dataset
uspto-grants-2010_08
Patent number
US07786309B2

Reaction notes

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