Ammonia → (R)-2-(4-Methanesulfonyl-3-methyl-pyridin-2-ylmethanesulfinyl)-1H-benzimidazole

HRID 1894985Notes

Reaction equation

HRID 1894985 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][N:8]=[C:7]([CH2:11][S:12]([C:15]2[NH:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[N:16]=2)(=O)=[O:13])[C:6]=1[CH3:24])(=[O:4])=[O:3].C([C@@](C([O-])=O)(O)[C@@](CC)(O)C([O-])=O)C.C(N(C(C)C)CC)(C)C.[O-]O.C1(C(C)C)C=CC=CC=1.N>O.O1CCCC1>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][N:8]=[C:7]([CH2:11][S@:12]([C:15]2[NH:16][C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[N:19]=2)=[O:13])[C:6]=1[CH3:24])(=[O:3])=[O:4]

Participants

8

Reactant 5

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 29414057diethyl-L(+)-tartrateHCID 53627471Cumen hydroperoxideHCID 866560874-Detrifluoroethoxy-4-methylsulfonyl Lansoprazole Sulfone

Product 1

HCID 67299194(R)-2-(4-Methanesulfonyl-3-methyl-pyridin-2-ylmethanesulfinyl)-1H-benzimidazoleYield 75.3%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

To a mixture of 2-(4-methanesulfonyl-3-methyl-pyridineylmethylsulfonyl)-1-H-benzimidazole (25 g), tetrahydrofuran (625 ml) and water (0.08 gm) was added (+)-diethyl-L-tartrate (31 gm) under nitrogen atmosphere and heated to 50 to 60° C. Subsequently, Ti(IV)isopropoxide (21.3 gm) was added to the reaction mixture at 50 to 60° C. and maintained at the same temperature for about 45-60 min. The reaction mixture was cooled to 20-25° C. and diisopropylethylamine (9.7 g) was added and maintained at the same temperature for 10-15 min. Cumene hydroperoxide (80% 15 ml) was then added to the reaction mixture and maintained at the same temperature for 2 hours. To the reaction mixture was added 10-12% aq. ammonia solution (100 ml) and maintained for 15 min. The layers were separated and 10-12% aq. ammonia solution (100 ml) was added to the organic layer at 20-25° C., maintained for 15 min and the steps repeated for two or three times. Combined all the aq. ammonia solution layers and cooled to 0-10° C. Adjusted the pH of the reaction mixture to 7.0 to 7.5 with acetic acid (125 ml) at 0 to 10° C. Distilled off the tetrahydrofuran traces at 40° C. under reduced pressure. Cooled the reaction mixture to 0 to 10° C. and maintained at the same temperature for about one to two hours. Filtered the solid and washed with DM water (50 ml) and dried to give 18 g of the title compound.

Workup

  1. temperaturemaintained at the same temperature for about 45-60 min
  2. temperatureThe reaction mixture was cooled to 20-25° C.
  3. temperaturemaintained at the same temperature for 10-15 min
  4. temperaturemaintained at the same temperature for 2 hours
  5. temperaturemaintained for 15 min
  6. customThe layers were separated
  7. addition10-12% aq. ammonia solution (100 ml) was added to the organic layer at 20-25° C.
  8. temperaturemaintained for 15 min
  9. temperaturecooled to 0-10° C
  10. customat 0 to 10° C
  11. distillationDistilled off the tetrahydrofuran
  12. customtraces at 40° C. under reduced pressure
  13. temperatureCooled the reaction mixture to 0 to 10° C.
  14. temperaturemaintained at the same temperature for about one to two hours
  15. filtrationFiltered the solid
  16. washwashed with DM water (50 ml)
  17. customdried

Sources & evidence

ORD record
ord-941c0762b04b489a82a8176c1f53ab43
Source dataset
uspto-grants-2013_08
Patent number
US08513427B2

Reaction notes

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