Hydrochloric Acid → HCID 18976185, compound

Participants

Reaction Steps

In 80 ml of anhydrous methanol was dissolved 23.85 g of the (+)-N-[3-(2-cyanoethyl)-1-(2-fluorophenyl)-2,3-dihydro-6-methoxy-2-oxo-1H-indol-3-yl]-3-isoquinolinecarboxamide crude product, and under ice cooling, a hydrochloric acid gas was passed through the solution until the gas was saturated. Thereafter, 1.71 ml of water was added to the solution. The reaction mixture was refluxed for 1 hour, cooled and then concentrated under reduced pressure. The residue was neutralized with an aqueous saturated sodium hydrogen carbonate solution and then extracted with ethyl acetate. The organic layer was separated, washed with water with a saturated sodium chloride solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (ethyl acetate:hexane (1:1, volume) as an eluant to afford 22.30 g of (+)-methyl 3-[l-(2-fluorophenyl)-2,3-dihydro-3-(3-isoquinolinyl)carbonylamino-6-methoxy-2-oxo-1H-indol-3-yl]propionate as a pale yellow amorphous solid (yield: 91% (from the product of Example 176 (2))). DI-MS (m/z) 513 (MH+), 426, 156, 128 (base). [α]D25 : +66.2° (c=0.402, chloroform).

Provenance & Evidence