Methyl formate → Omeprazole

HRID 861438Notes

Reaction equation

HRID 861438 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 12016905HCID 12016905, compound

Product 1

HCID 4594OmeprazoleYield 81%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

0.76 g (1.5 mmol) of the more hydrophilic diastereomer of 6-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1-[(S)-mandeloyloxymethyl]-1H-benzimidazole was dissolved in 50 ml methanol. A solution of 0.12 mg (3.0 mmol) sodium hydroxide in 1.5 ml water was added, and after 10 minutes the mixture was evaporated on a rotavapor. The residue was partitioned between 25 ml water and 25 ml dichloromethane. The organic solution was extracted with 25 ml water and to the combined aqueous solutions was added 200 μl (3.2 mmol) methyl formate. After 15 minutes the mixture was extracted with 3×25 ml dichloromethane. The organic solution was dried over Na2SO4 and then evaporated. There was obtained 0.42 g (81%) of the title compound as a colorless syrup. The optical purity (e.e.) which was analyzed by chiral column chromatography was 98%. [α]D20 =+157° (c=0.5%, chloroform).

Workup

  1. customafter 10 minutes the mixture was evaporated on a rotavapor
  2. customThe residue was partitioned between 25 ml water and 25 ml dichloromethane
  3. extractionThe organic solution was extracted with 25 ml water and to the combined aqueous solutions
  4. extractionAfter 15 minutes the mixture was extracted with 3×25 ml dichloromethane
  5. dry with materialThe organic solution was dried over Na2SO4
  6. customevaporated

Sources & evidence

ORD record
ord-24660d49337b4210a645998e635cf04d
Source dataset
uspto-grants-1998_02
Patent number
US05714504

Reaction notes

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