Hydrochloric Acid → (4'S,5'R)-6''-chloro-4'-(3-chloro-2-fluorophenyl)-4,4-dimethyl-2''-oxo-1'',2''-dihydrodispiro[cyclohexane-1,2'-pyrrolidine-3',3''-indole]-5'-carboxylic acid

Participants

Reaction Steps

1N sodium hydroxide solution (50 ml, 50 mmol) was added to a methanol (250 ml) solution of the compound (15.7 g, 23.4 mmol) obtained in Step 1 of Example 1 and the resulting mixture was heated to reflux overnight. After cooling, methanol (500 ml) and water (200 ml) were added to the reaction mixture and then the resulting mixture was neutralized by addition of 1N hydrochloric acid (50 ml) under ice cooling. Cerium (IV) diammonium nitrate (26.9 g, 49.1 mmol) was added under ice cooling, the resulting mixture was stirred for 20 minutes, then potassium carbonate (13.6 g, 98.3 mmol) was added and the resulting mixture was further stirred for 30 minutes. Insoluble matter was removed by filtration through celite and the filtrate was concentrated under reduced pressure. The residue was diluted with water, followed by extraction with ethyl acetate. The aqueous layer was further subjected to extraction with chloroform:methanol [5:1 (v/v)], the organic layers were combined and dried over anhydrous sodium sulfate, then the solvent was evaporated under reduced pressure and the residue was dried to give 6.54 g (57%) of the title compound as a pale yellow solid.

Provenance & Evidence