Sodium Hydroxide → HCID 18976143, compound

HRID 2393612Notes

Reaction equation

HRID 2393612 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=2)[C:10]([CH2:32][CH2:33][C:34]([O:36]C)=[O:35])([NH:19][C:20]([C:22]2[N:23]=[CH:24][C:25]3[C:30]([CH:31]=2)=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:21])[C:9]1=[O:38].[OH-].[Na+]>CO>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=2)[C:10]([CH2:32][CH2:33][C:34]([OH:36])=[O:35])([NH:19][C:20]([C:22]2[N:23]=[CH:24][C:25]3[C:30]([CH:31]=2)=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:21])[C:9]1=[O:38]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 18976185HCID 18976185, compound

Product 1

HCID 18976143HCID 18976143, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 62.53 g of (+)-methyl 3-[1-(2-fluorophenyl)-2,3-dihydro-3-(3-isoquinolinyl)carbonylamino-6-methoxy-2-oxo-1H-indol-3-yl]propionate, 56.78 ml of a 3N--NaOH aqueous solution and 576 ml of methanol was stirred at room temperature overnight under ice cooling. The reaction mixture was concentrated under reduced pressure, and the residue was made acidic with an aqueous 15% citric acid solution and extracted with ethyl acetate. The organic layer was collected by separation and washed with water successively with water and a saturated sodium chloride solution, and treated with 15 g of activated charcoal was added to the organic layer, and the mixture was dried over anhydrous sodium sulfate. After insolubles were removed by filtration, the filtrate was concentrated under reduced pressure to afford (+)-3-[1-(2-fluorophenyl)-2,3-dihydro-3-(3-isoquinolinyl)carbonylamino-6-methoxy-2-oxo-1H-indol-3-yl]propionic acid as an oily product. [α]D25 : +80.3° (c=0.426, chloroform). To the product obtained above were added 7.36 g of sodium carbonate and 200 ml of water. After the solution was concentrated to dryness under reduced pressure, the residue was dissolved in 500 ml of acetonitrile under heating, and the insolubles were filtered off. After cooling, the crystals precipitated from the filtrate were collected by filtration to afford 60.07 g of (+)-sodium 3-[1-(2-fluorophenyl)-2,3-dihydro-3-(3-isoquinolinyl)carbonylamino-6-methoxy-2-oxo-1H-indol-3-yl]propionate as a colorless solid (yield: 95%). Melting point: 206° to 211° C. FAB-MS (m/z): 522 (MH+), 177, 23 (base). [α]D25 : +89.7° (c=0.406, methanol).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. extractionextracted with ethyl acetate
  3. customThe organic layer was collected by separation
  4. washwashed with water successively with water
  5. additiona saturated sodium chloride solution, and treated with 15 g of activated charcoal
  6. additionwas added to the organic layer
  7. dry with materialthe mixture was dried over anhydrous sodium sulfate
  8. customAfter insolubles were removed by filtration
  9. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-9f892334512b424db89b05881b683244
Source dataset
uspto-grants-1998_09
Patent number
US05807883

Reaction notes

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