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

HRID 1728095Notes

Reaction equation

HRID 1728095 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:28])[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](=[CH2:27])[CH2:25][CH3:26])[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:28])[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](=[CH2:27])[CH2:25][CH3:26])[C:5]2=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 77581292racemic (2'R,3R,4'S)-6-bromo-4'-(3-chlorophenyl)-2'-(1-methylene-propyl)-2,3-dihydro-2,6'-dioxo spiro[indole-3,3'-piperidine] 1-methoxyethyl trimethylsilane

Product 1

HCID 76567900racemic (2'R,3R,4'S)-6-bromo-4'-(3-chlorophenyl)-2'-(1-methylene-propyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 81.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of racemic (2′R,3R,4′S)-6-bromo-4′-(3-chlorophenyl)-2′-(1-methylene-propyl)-2,3-dihydro-2,6′-dioxospiro[indole-3,3′-piperidine]-1-methoxyethyl trimethylsilane (50 mg, 0.08 mmol) prepared in example 161b in dichloromethane (5 mL) was added trifluoroacetic acid (5 mL). The reaction mixture was stirred at room temperature for 0.5 h. After removing the solvent, the residue was dissolved in methanol (2 mL). To the resulting solution was added N,N′-diisopropylethylamine (1 mL). The reaction tube was then 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-methylene-propyl)-spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as solid (30 mg).

Workup

  1. customAfter removing the solvent
  2. dissolutionthe residue was dissolved in methanol (2 mL)
  3. additionTo the resulting solution was added N,N′-diisopropylethylamine (1 mL)
  4. temperatureThe reaction tube was then 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-30d2b1e0e3d341169aeacc8ca961823c
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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