Hydrochloric Acid → (1R,2R)-3-((2-(4-cyanophenyl)-5'-fluoro-2-isopropyl-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)methyl)benzoic acid

Participants

Reaction Steps

To a solution of (1S,2S) and (1R,2R)-methyl-3-((2-(4-cyanophenyl)-5′-fluoro-2-isopropyl-2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)methyl)benzoate (500 mg, 1.1 mmol) in tetrahydrofuran (10 mL) was added 30% sodium hydroxide in water (3 mL) at room temperature and the mixture was stirred at that temperature for 16 hours. The mixture was neutralized with 2 N aqueous hydrochloric acid solution, diluted with ethyl acetate (50 mL), washed with water, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% trifluoro-acetic acid in water) afforded the title compound (270 mg, 59.5%) as a white solid: LC/MS m/e calcd. for C28H23FN2O3: 454, observed (M+H)+: 455.2 1H NMR (400 MHz, MeOD-d4) δppm 7.97 (s, 1 H), 7.94 (d, J=7.83 Hz, 1 H), 7.85 (dd, J=7.96, 1.64 Hz, 1 H), 7.67 (dd, J=7.96, 1.39 Hz, 1 H), 7.61 (d, J=7.58 Hz, 1 H), 7.48 (q, I=7.83 Hz, 2 H), 6.74-6.86 (m, 3 H), 5.28 (d, I=15.92 Hz, 1 H), 5.17 (dd, J=8.72, 2.40 Hz, 1 H), 4.97 (d, J=16.17 Hz, 1 H), 3.04 (dt, J=13.64, 6.82 Hz, 1 H), 2.23-2.28 (m, 1 H), 2.20-2.23 (m, 1 H), 0.92 (d, J=7.07 Hz, 3 H), 0.81 (d, J=6.82 Hz, 3 H).

Provenance & Evidence