Piperidine → Spiro(cyclopropane-1,3'-indolin)-2'-one

Participants

Reaction Steps

3-(((1S,2R)-2-(4-chlorophenyl)-2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)methyl)benzoic acid and 3-(((1R,2S)-2-(4-chlorophenyl)-2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)methyl)benzoic acid (prepared according to Scheme 1) (60 mg, 0.15 mmol), 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl) (44 mg, 0.225 mmol 1.5 mmol), anhydrous 1-Hydroxybenzotriazole (HOBt) (31 mg, 0.225 mmol) and piperidine (15 mg, 0.18 mmol) were dissolved in DMF. The mixture was stirred at room temperature for 14 hours. (1R,2S) and (1S,2R)-2-(4-chlorophenyl)-1′-(3-(piperidine-1-carbonyebenzyl)spiro[cyclopropane-1,3′-indolin]-2′-one were purified by preparative HPLC as a white solid (42 mg, 60%). LC/MS m/e calcd. for C29H27ClN2O2: 470, observed (M+H)+: 471.2 1H NMR (400 MHz, MeOD-d4) δppm 1.41 (br. s., 2 H) 1.67 (br. s., 4 H) 2.19-2.30 (m, 2 H) 3.28 (br.s., 2 H) 3.30 (s, 1 H) 3.69 (br. s., 2 H) 5.14 (s, 2 H) 6.11 (d, J=7.33 Hz, 1 H) 6.74 (t, J=7.20 Hz, 1 H) 6.91 (d, J=7.83 Hz, 1 H) 7.03-7.15 (m, 1 H) 7.20-7.28 (m, 2 H) 7.28-7.38 (m, 4 H) 7.43-7.57 (m, 2 H).

Provenance & Evidence