Hydrochloric Acid → rac-(2'S,3'S,4'S)-6-chloro-2'-(3-chloro-2-fluoro-phenyl)-4'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-1'-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amide

Participants

Reaction Steps

To a solution of rac-(2′S,3′S,4′S)-6-chloro-2′-(3-chloro-2-fluoro-phenyl)-4′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-1′-carbonyl chloride (0.14 g, 0.28 mmol) in tetrahydrofuran (5 mL) was added 2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethylamine prepared in Example 7 (49 mg, 0.34 mmol) and triethylamine (0.078 mL, 0.56 mmol). The reaction mixture was stirred at room temperature for 1 h. An aqueous HCl solution (1 N, 2 mL) was added. The reaction mixture was stirred at room temperature for 0.5 h. The solvents were removed and the residue was partitioned between ethyl acetate and saturated aqueous NaHCO3 solution. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water, brine, dried over MgSO4, and concentrated. The residue was triturated with dichlormethane and hexanes to give rac-(2′S,3′S,4′S)-6-chloro-2′-(3-chloro-2-fluoro-phenyl)-4′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-1′-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amide as a white solid (Yield 75 mg, 50%).

Provenance & Evidence