Hydrochloric Acid → 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 [1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-amide

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 {1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-amide (0.1 g, 0.15 mmol) in tetrahydrofuran (5 mL) was added aqueous HCl solution (1N, 5 mL, 5 mmol). The reaction mixture was stirred at room temperature for 0.5 h. The mixture was concentrated. The residue was partitioned between ethyl acetate and aqueous saturated NaHCO3 solution. The organic layer was separated, washed with water, brine, dried over Na2SO4, then concentrated. The residue was purified by chromatography (silica gel, 25-100% of EtOAc in hexanes) 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 [1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-amide as a white solid (Yield, 45 mg, 54%).

1. concentrationThe mixture was concentrated
2. customThe residue was partitioned between ethyl acetate and aqueous saturated NaHCO3 solution
3. customThe organic layer was separated
4. washwashed with water, brine
5. dry with materialdried over Na2SO4
6. concentrationconcentrated
7. customThe residue was purified by chromatography (silica gel, 25-100% of EtOAc in hexanes)
8. customto give

ORD record

ord-d630f2cb4b684f14a121be926ab18caf

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08088815B2