Hydrochloric Acid → 6-chloro-4'-[5-chloro-2-(3-methanesulfonylamino-2,2-dimethyl-3-oxo-propoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

Participants

Reaction Steps

A solution of racemic (2′S,3S,4′R)-6-chloro-4′-[5-chloro-2-(2-hydroxycarbonyl-2-methyl-propoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (300 mg, 0.5 mmol) prepared in Example 20f and CDI (160 mg, 1 mmol) in DMF (2 mL) was heated at 60° C. for 2 h. Then to this solution was added a mixture of methanesulfonamide (285 mg, 3 mmol) and NaH (120 mg, 60%, 3 mmol) in DMF (1 mL), which had been mixed and stirred at room temperature for 2 h. After the resulting mixture was stirred at room temperature for 1 h, it was poured into water and the aqueous solution was acidified to “pH” 1-2 by addition of concentrated HCl. After the aqueous phase was extracted with EtOAc twice, the combined organic layers were dried over anhydrous Na2SO4, concentrated and the residue was purified by flash column to give the title compound as a white solid (70 mg).

Provenance & Evidence