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

HRID 1728097Notes

Reaction equation

HRID 1728097 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:29])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[NH:12][CH:11]3[C:24]3([CH2:27][CH3:28])[CH2:26][CH2:25]3)[C:5]2=[CH:4][CH:3]=1.COC([Si](C)(C)C)C.FC(F)(F)C(O)=O>ClCCl>[Br:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:29])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[NH:12][CH:11]3[C:24]3([CH2:27][CH3:28])[CH2:25][CH2:26]3)[C:5]2=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 77580691racemic (2'R,3R,4'S)-6-bromo-4'-(3-chlorophenyl)-2'-(1-ethyl-cyclopropyl)-2,3-dihydro-2,6'-dioxo spiro[indole-3,3'-piperidine] 1-methoxyethyl trimethylsilane

Product 1

HCID 76568061racemic (2'R,3R,4'S)-6-bromo-4'-(3-chlorophenyl)-2'-(1-ethyl-cyclopropyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  1. customThen the solvent was removed in vacuo
  2. dissolutionThe residue was dissolved in methanol (2 mL)
  3. additionTo the resulting solution was added N,N′-diisopropylethylamine (1 mL)
  4. temperatureThe mixture was heated at 135 ° C. for 20 min
  5. concentrationThe reaction mixture was concentrated
  6. customthe residue was purified by Prep-HPLC

Sources & evidence

ORD record
ord-6c704449e79147e1aa0badfd1f36e787
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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