Sodium Hydroxide → Tegoprazan

HRID 2239304Notes

Reaction equation

HRID 2239304 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C@@H:4]([O:13][C:14]1[C:22]3[N:21]=[C:20]([CH3:23])[N:19](S(C4C=CC(C)=CC=4)(=O)=O)[C:18]=3[CH:17]=[C:16]([C:34]([N:36]([CH3:38])[CH3:37])=[O:35])[CH:15]=1)[CH2:5][CH2:6][O:7]2.[OH-].[Na+]>O1CCCC1.CC(O)C.C(OCC)(=O)C>[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C@@H:4]([O:13][C:14]1[C:22]3[N:21]=[C:20]([CH3:23])[NH:19][C:18]=3[CH:17]=[C:16]([C:34]([N:36]([CH3:37])[CH3:38])=[O:35])[CH:15]=1)[CH2:5][CH2:6][O:7]2

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 68574320N-tosyl Tegoprazan

Product 1

HCID 23582846TegoprazanYield 87.8%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (−)-4-[((4S)-5,7-difluoro-3,4-dihydro-2H-chromen-4-yl)oxy]-N,N,2-trimethyl-1-[(4-methylphenyl)-sulfonyl]-1H-benzimidazole-6-carboxamide (24.2 g, 44.7 mmol, STEP 9) in tetrahydrofuran (65 mL) and 2-propanol (220 mL) was added 2M sodium hydroxide aqueous solution (220 mL, 440 mmol) at room temperature. After stirring at room temperature for 4 hours, the mixture was diluted with ethyl acetate (1.20 L) and washed with saturated ammonium chloride aqueous solution (500 mL). The organic solution was dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography on amino gel (ethyl acetate:methanol gradient elution from 50:1 to 20:1) to afford the title compound as a white solid (15.2 g, 87%, >99% ee).

Workup

  1. washwashed with saturated ammonium chloride aqueous solution (500 mL)
  2. dry with materialThe organic solution was dried over magnesium sulfate
  3. concentrationconcentrated in vacuum
  4. customThe residue was purified by column chromatography on amino gel (ethyl acetate:methanol gradient elution from 50:1 to 20:1)

Sources & evidence

ORD record
ord-ef759a7d7fb240c2a54aeebe9b89d931
Source dataset
uspto-grants-2010_05
Patent number
US07723321B2

Reaction notes

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