Phosgene → 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 4-methoxycarbonyl-benzyl ester

Participants

Reaction Steps

To a solution of methyl 4-(hydroxymethyl)benzoate (20 mg, 0.12 mmol) in tetrahydrofuran (3 mL) was added a toluene solution (Aldrich, 20%) of phosgene (0.25 mL, 0.48 mmol) dropwise via a syringe. The reaction mixture was stirred at room temperature for 1 h, then the solvents were removed. The residue was dissolved into tetrahydrofuran (3 mL), and rac-(2′S,3′S,4′S)-6-chloro-2′-(3-chloro-2-fluoro-phenyl)-4′-(2,2-dimethyl-propyl)-1H-spiro[indole-3,3′-pyrrolidin]-2-one prepared in Example 6 (56 mg, 0.13 mmol) and triethylamine (0.04 mL, 0.29 mmol) were added sequentially. The reaction mixture was stirred at room temperature for 18 h. The solvents were removed, and the residue was partitioned between ethyl acetate and water. 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 purified by chromatography (35% EtOAc in 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 4-methoxycarbonyl-benzyl ester as a white solid (Yield 55 mg, 68%).

Provenance & Evidence