Trifluoroacetic acid → racemic (2'R,3R,4'S)-6-bromo-4'-(3-chlorophenyl)-2'-(1-ethyl-cyclopropyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

Participants

Reaction Steps

To a solution of racemic (2′R,3R,4′S)-6-bromo-4′-(3-chlorophenyl)-2′-(1-ethyl-cyclopropyl)-2,3-dihydro-2,6′-dioxospiro[indole-3,3′-piperidine]-1-methoxyethyl trimethylsilane (48 mg, 0.079 mmol) prepared in example 162a in dichloromethane (5 mL) was added trifluoroacetic acid (5 mL). The mixture was stirred at room temperature for 5 h. Then the solvent was removed in vacuo. The residue was dissolved in methanol (2 mL). To the resulting solution was added N,N′-diisopropylethylamine (1 mL). The mixture was heated at 135 ° C. for 20 min. The reaction mixture was concentrated and the residue was purified by Prep-HPLC to obtain racemic (2′R,3R,4′S)-6-bromo-4′-(3-chlorophenyl)-2′-(1-ethyl-cyclopropyl)-spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione. The racemic compound was separated by chiral column chromatography to obtain chiral (2R,3R,4′S)-6-bromo-4′-(3-chlorophenyl)-2′-(1-ethyl-cyclopropyl)-spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (4.5 mg) and chiral (2S,3S,4′R)-6-bromo-4′-(3-chlorophenyl)-2′-(1-ethyl-cyclopropyl)-spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (4.5 mg).

Provenance & Evidence