Sodium Hydroxide → HCID 18976143, compound

Participants

Reaction Steps

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).

Provenance & Evidence