Methyl Anthranilate → rac-4-{[(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carbonyl]-amino}-benzoic acid methyl ester

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)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid trifluoroacetic acid (0.86 g, 1.48 mmol) in dichloromethane (20 mL) was added diisopropylethylamine (1.53 g, 11.9 mmol), diphenylphosphinic chloride (Aldrich) (1.41 g, 5.94 mmol) respectively. The mixture was stirred at room temperature for 0.5 h, then methyl aminobenzoate (Acros) (0.22 g, 1.48 mmol) was added. The reaction mixture was stirred at room temperature for 20 h. The mixture was concentrated. The residue was partitioned between ethyl acetate and water. The organic layer was separated, washed with water, brine, dried over Na2SO4, then concentrated. The residue was purified by chromatography (3-10% of EtOAc in CH2Cl2) to give rac-4-{[(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carbonyl]-amino}-benzoic acid methyl ester as a off white solid (0.34 g, 38%).

Provenance & Evidence