Hydrogen Peroxide → 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 (2-carbamoyl-pyrimidin-5-yl)-amide

Temperature

0 °C

To the 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 (2-cyano-pyrimidin-5-yl)-amide (30 mg, 0.05 mmol) prepared in Example 184 in DMSO (0.2 mL) at 0° C. was added an aqueous solution (30% Aldrich) of H2O2 (0.09 g, 0.8 mmol), then aqueous solution (1N) of NaOH (0.3 mL, 0.3 mmol) was added dropwise. The reaction mixture was stirred at 0° C. for 1 h. The mixture was partitioned between ethyl acetate and saturated aqueous Na2SO3 solution. The organic layer was separated, washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (50-100% EtOAc in dichloromethane) to give 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 (2-carbamoyl-pyrimidin-5-yl)-amide as a white solid (Yield 8 mg, 26%)

1. customThe mixture was partitioned between ethyl acetate and saturated aqueous Na2SO3 solution
2. customThe organic layer was separated
3. washwashed with water, brine
4. dry with materialdried over MgSO4
5. concentrationconcentrated
6. customThe residue was purified by chromatography (50-100% EtOAc in dichloromethane)

ORD record

ord-3f4b1bfb9e5a44f7aedfe3702d4be44a

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08088815B2