Diphenylphosphinic chloride → rac-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-7-fluoro-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid [4-(2-hydroxy-ethoxy)-2-methoxy-phenyl]-amide

Participants

Reaction Steps

To a solution of rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-5-fluoro-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid trifluoroacetic acid prepared in Example 174 (0.2 g, 0.3 mmol) in dichloromethane (3 mL) was added diisopropylethylamine (0.2 g, 1.7 mmol), diphenylphosphinic chloride (Aldrich) (0.16 g, 0.67 mmol) respectively. The mixture was stirred at room temperature for 8 min, then 40[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-2-methoxy-phenylamine prepared in Example 132 (0.15 g, 0.5 mmol) was added. The reaction mixture was stirred at room temperature for 2 h. The mixture was concentrated. The residue was dissolved into tetrahydrofuran (3 mL), and an aqueous solution (1N) of HCl (1 mL) was added. The reaction mixture was stirred at room temperature for 1 h, then concentrated. The residue was partitioned between ethyl acetate and aqueous saturated NaHCO3 solution. The organic layer was separated, and aqueous layer was extracted with ethyl acetate twice. The combined organic extract was washed with water, brine, dried over Na2SO4, then concentrated. The residue was purified by chromatography (0-50% of EtOAc in CH2Cl2) to give rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-7-fluoro-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid [4-(2-hydroxy-ethoxy)-2-methoxy-phenyl]-amide as a yellow solid (85 mg, 39%).

Provenance & Evidence