Racemic (2'R,3R,4'S)-1'-(aminocarbonyl-methyl)-6-bromo-4'-(3-chlorophenyl)-2'-(1-methylene-propyl)-2,3-dihydro-2,6'-dioxo-spiro[indole-3,3'-piperidine] 1-methoxyethyl trimethylsilane → racemic (2'R,3R,4'S)-1'-(aminocarbonyl-methyl)-6-bromo-4'-(3-chlorophenyl)-2'-(1-methylene-propyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 1728161Notes

Reaction equation

HRID 1728161 reaction equation
[NH2:1][C:2]([CH2:4][N:5]1[C:10](=[O:11])[CH2:9][CH:8]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=2)[C:7]2([C:26]3[C:21](=[CH:22][C:23]([Br:27])=[CH:24][CH:25]=3)[NH:20][C:19]2=[O:28])[CH:6]1[C:29](=[CH2:32])[CH2:30][CH3:31])=[O:3].COC([Si](C)(C)C)C>FC(F)(F)C(O)=O.ClCCl>[NH2:1][C:2]([CH2:4][N:5]1[C:10](=[O:11])[CH2:9][CH:8]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=2)[C:7]2([C:26]3[C:21](=[CH:22][C:23]([Br:27])=[CH:24][CH:25]=3)[NH:20][C:19]2=[O:28])[CH:6]1[C:29](=[CH2:32])[CH2:30][CH3:31])=[O:3]

Participants

4

Reactant 1

HCID 77580671Racemic (2'R,3R,4'S)-1'-(aminocarbonyl-methyl)-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 76567866racemic (2'R,3R,4'S)-1'-(aminocarbonyl-methyl)-6-bromo-4'-(3-chlorophenyl)-2'-(1-methylene-propyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 25.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

Racemic (2′R,3R,4′S)-1′-(aminocarbonyl-methyl)-6-bromo-4′-(3-chlorophenyl)-2′-(1-methylene-propyl)-2,3-dihydro-2,6′-dioxo-spiro[indole-3,3′-piperidine]-1-methoxyethyl trimethylsilane (350 mg) was dissolved in a solution of trifluoroacetic acid (5 mL) and dichloromethane (5 mL). The reaction mixture was stirred at room temperature for 0.5 h. The reaction mixture was concentrated. The residue was redissolved in a mixture of methanol (3 ml) and DIPEA. The reaction tube was then placed into the cavity of a focused monomode microwave reactor and the contents of the flask were irradiated for 30 min at 120° C. The reaction mixture was concentrated and the residue was concentrated and the residue was purified by Prep-HPLC to obtain 70 mg product.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionThe residue was redissolved in a mixture of methanol (3 ml) and DIPEA
  3. customThe reaction tube was then placed into the cavity of a focused monomode microwave reactor
  4. customthe contents of the flask were irradiated for 30 min at 120° C
  5. concentrationThe reaction mixture was concentrated
  6. concentrationthe residue was concentrated
  7. customthe residue was purified by Prep-HPLC

Sources & evidence

ORD record
ord-d08f613dc01044ce978b6e90270ebaf7
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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