Tetrahydrofuran → HCID 9984105, compound

HRID 2096080Notes

Reaction equation

HRID 2096080 reaction equation
C(N(CC)CC)C.[C:8](=[O:43])([O:12][CH2:13][CH2:14][N:15]([C:17]([N:19]1[C:23]2[CH:24]=[C:25](OC)[CH:26]=[CH:27][C:22]=2[N:21]=[C:20]1[S:30]([CH2:32][C:33]1[C:38]([CH3:39])=[C:37]([O:40][CH3:41])[C:36]([CH3:42])=[CH:35][N:34]=1)=[O:31])=[O:18])[CH3:16])[O:9][CH2:10][CH3:11].[O:44]1CCC[CH2:45]1>>[C:8](=[O:43])([O:12][CH2:13][CH2:14][N:15]([C:17]([N:19]1[C:23]2[CH:24]=[CH:25][C:26]([O:44][CH3:45])=[CH:27][C:22]=2[N:21]=[C:20]1[S:30]([CH2:32][C:33]1[C:38]([CH3:39])=[C:37]([O:40][CH3:41])[C:36]([CH3:42])=[CH:35][N:34]=1)=[O:31])=[O:18])[CH3:16])[O:9][CH2:10][CH3:11]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 10436645HCID 10436645, compound

Product 1

HCID 9984105HCID 9984105, compound

Procedure

To a solution of bis(trichloromethyl)carbonate (0.291 g) in tetrahydrofuran (10 mL) was added dropwise a solution of pyridine (0.243 mL) in tetrahydrofuran (1 mL) under ice-cooling. The reaction solution was stirred for 1 hr under ice-cooling, and ethyl 2-(methylamino)ethyl carbonate hydrochloride (0.551 g) obtained in Reference Synthetic Example 14 was added thereto. A solution of triethylamine (0.418 mL) in tetrahydrofuran (1 mL) was added dropwise, and stirred at room temperature for 2 hrs. The reaction solution was concentrated under reduced pressure, and to the residue was added water (15 mL), and then extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with saturated brine (15 mL), and dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure, and the residue was dissolved in tetrahydrofuran (10 mL). To the solution were added 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole (0.817 g), triethylamine (0.661 mL) and 4-dimethylaminopyridine (0.012 g), and stirred at 60° C. for 12 hrs. The reaction solution was concentrated under reduced pressure, and to the residue was added water (20 mL), and extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with saturated brine (15 mL), and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was purified with basic silica gel column chromatography (eluted with ethyl acetate:hexane=1:2, then 1:1) to give a mixture of 3:2 of title compound and ethyl 2-[[[6-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-1H-benzimidazol-1-yl]carbonyl](methyl)amino]ethyl carbonate as pale yellow amorphous solid (0.92 g).

Workup

  1. additionwas added
  2. concentrationThe reaction solution was concentrated under reduced pressure
  3. additionto the residue was added water (15 mL)
  4. extractionextracted with ethyl acetate (50 mL)
  5. washThe ethyl acetate layer was washed with saturated brine (15 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationThe solution was concentrated under reduced pressure
  8. dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
  9. additionTo the solution were added 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole (0.817 g), triethylamine (0.661 mL) and 4-dimethylaminopyridine (0.012 g)
  10. stirringstirred at 60° C. for 12 hrs
  11. concentrationThe reaction solution was concentrated under reduced pressure
  12. additionto the residue was added water (20 mL)
  13. extractionextracted with ethyl acetate (50 mL)
  14. washThe ethyl acetate layer was washed with saturated brine (15 mL)
  15. dry with materialdried over anhydrous magnesium sulfate
  16. concentrationAfter concentrating under reduced pressure
  17. customthe residue was purified with basic silica gel column chromatography (
  18. washeluted with ethyl acetate
  19. customhexane=1:2, then 1:1) to give

Sources & evidence

ORD record
ord-622e9397f1434e6994a4ed61c51349af
Source dataset
uspto-grants-2013_05
Patent number
US08449911B2

Reaction notes

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