Methyl formate → Omeprazole

HRID 1814219Notes

Reaction equation

HRID 1814219 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[N:10]=[C:9]([S:11]([CH2:13][C:14]3[C:19]([CH3:20])=[C:18]([O:21][CH3:22])[C:17]([CH3:23])=[CH:16][N:15]=3)=[O:12])[N:8](COC(=O)[C@@H](C3C=CC=CC=3)O)[C:7]=2[CH:36]=1.[OH-].[Na+].C(OC)=O>CO.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[NH:10][C:9]([S:11]([CH2:13][C:14]3[C:19]([CH3:20])=[C:18]([O:21][CH3:22])[C:17]([CH3:23])=[CH:16][N:15]=3)=[O:12])=[N:8][C:7]=2[CH:36]=1

Participants

6

Reactant 3

HCID 7865Methyl formateHCID 14798Sodium HydroxideHCID 54111443HCID 54111443, compound

Product 1

HCID 4594OmeprazoleYield 77%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

0.23 g (0.45 mmol) of the more hydrophilic diastereomer of 6-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1-[(R)-mandeloyloxymethyl]-1H-benzimidazole was dissolved in 15 ml methanol. A solution of 36 mg (0.9 mmol) sodium hydroxide in 0.45 ml water was added, and after 10 minutes the mixture was evaporated on a rotavapor. The residue was partitioned between 15 ml water and 15 ml dichloromethane. The organic solution was extracted with 15 ml water and to the combined aqueous solutions was added 85 μL (1.4 mmol) methyl formate. After 15 minutes the mixture was extracted with 3×10 ml dichloromethane. The organic solution was dried over Na2SO4 and then evaporated. There was obtained 0.12 g (77%) of the title compound as a colorless syrup. The optical purity (e.e.) which was analyzed by chiral column chromatography was 94%. [α]D20=−155° (c=0.5%, chloroform).

Workup

  1. customafter 10 minutes the mixture was evaporated on a rotavapor
  2. customThe residue was partitioned between 15 ml water and 15 ml dichloromethane
  3. extractionThe organic solution was extracted with 15 ml water and to the combined aqueous solutions
  4. extractionAfter 15 minutes the mixture was extracted with 3×10 ml dichloromethane
  5. dry with materialThe organic solution was dried over Na2SO4
  6. customevaporated

Sources & evidence

ORD record
ord-ece11971df274b3fbd99c89d377eb49e
Source dataset
uspto-grants-2005_04
Patent number
US06875872B1

Reaction notes

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