Water → racemic (2'S,3S,4'R)-6-chloro-1'-(3-chloro-propyl)-2'-(3-chlorophenyl)-4'-(5-fluoro-2-methyl-phenyl)-2,3-dihydro-2,6'-dioxospiro[indole-3,3'-piperidine] 1-methoxyethyl trimethylsilane

HRID 1728084Notes

Reaction equation

HRID 1728084 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:32])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=4[CH3:23])[CH2:14][C:13](=[O:24])[NH:12][CH:11]3[C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[CH:26]=3)[C:5]2=[CH:4][CH:3]=1.[CH3:33][O:34][CH:35]([Si:37]([CH3:40])([CH3:39])[CH3:38])[CH3:36].[H-].[Li+].[Cl:43][CH2:44][CH2:45][CH2:46]Br.O>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:32])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=4[CH3:23])[CH2:14][C:13](=[O:24])[N:12]([CH2:46][CH2:45][CH2:44][Cl:43])[CH:11]3[C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[CH:26]=3)[C:5]2=[CH:4][CH:3]=1.[CH3:33][O:34][CH:35]([Si:37]([CH3:40])([CH3:39])[CH3:38])[CH3:36]

Participants

6

Reactant 4

HCID 962WaterHCID 80061-Bromo-3-chloropropaneHCID 62714Lithium hydrideHCID 775809006-Chloro-2'-(3-chlorophenyl)-4'-(5-fluoro-2-methyl-phenyl)-2,3-dihydro-2,6'-dioxo spiro[indole-3,3'-piperidine] 1-methoxyethyl trimethylsilane

Product 1

HCID 77581272racemic (2'S,3S,4'R)-6-chloro-1'-(3-chloro-propyl)-2'-(3-chlorophenyl)-4'-(5-fluoro-2-methyl-phenyl)-2,3-dihydro-2,6'-dioxospiro[indole-3,3'-piperidine] 1-methoxyethyl trimethylsilaneYield 24.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Racemic (2′S,3S,4′R)-6-chloro-2′-(3-chlorophenyl)-4′-(5-fluoro-2-methyl-phenyl)-2,3-dihydro-2,6′-dioxospiro[indole-3,3′-piperidine]-1-methoxyethyl trimethylsilane (0.40 g, 0.67 mmol) prepared in example 146a was reacted with LiH (0.13 g, 16.70 mmol) and 1-chloro-3-bromo-propane (0.63 g, 4.01 mmol) in N,N-dimethyl-formamide (3 mL), a catalytic amount of KI. After the solution was stirred overnight, the solution was poured into water. The water layer was extracted with ethyl acetate and the combined organic layers were dried, concentrated to obtain the crude product. The crude product was purified by chromatography to give racemic (2′S,3S,4′R)-6-chloro-1′-(3-chloro-propyl)-2′-(3-chlorophenyl)-4′-(5-fluoro-2-methyl-phenyl)-2,3-dihydro-2,6′-dioxospiro[indole-3,3′-piperidine]-1-methoxyethyl trimethylsilane as a yellow solid (Yield: 0.11 g, 24%).

Workup

  1. extractionThe water layer was extracted with ethyl acetate
  2. customthe combined organic layers were dried
  3. concentrationconcentrated
  4. customto obtain the crude product
  5. customThe crude product was purified by chromatography

Sources & evidence

ORD record
ord-24e953df39c14aec91991c65e95b2061
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

Loading…