Lithium hydride → 6-Chloro-4'-(3-chloro-phenyl)-1'-(3-chloro-propyl)-2'-(2,3-difluoro-6-isopropoxy-phenyl)-2,3-dihydro-2,6'-dioxo spiro[indole-3,3'-piperidine] 1-methoxyethyl trimethylsilane

HRID 1728022Notes

Reaction equation

HRID 1728022 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:36])[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[C:29]([O:30][CH:31]([CH3:33])[CH3:32])=[CH:28][CH:27]=[C:26]([F:34])[C:25]=3[F:35])[C:5]2=[CH:4][CH:3]=1.[CH3:37][O:38][CH:39]([Si:41]([CH3:44])([CH3:43])[CH3:42])[CH3:40].[H-].[Li+].[Cl:47][CH2:48][CH2:49][CH2:50]I>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:36])[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])[N:12]([CH2:50][CH2:49][CH2:48][Cl:47])[CH:11]3[C:24]3[C:29]([O:30][CH:31]([CH3:33])[CH3:32])=[CH:28][CH:27]=[C:26]([F:34])[C:25]=3[F:35])[C:5]2=[CH:4][CH:3]=1.[CH3:37][O:38][CH:39]([Si:41]([CH3:44])([CH3:43])[CH3:42])[CH3:40]

Participants

5

Reactant 3

HCID 62714Lithium hydrideHCID 813631-Chloro-3-iodopropaneHCID 775806616-Chloro-4'-(3-chlorophenyl)-2'-(2,3-difluoro-6-isopropoxy-phenyl)-2,3-dihydro-2,6'-dioxo spiro[indole-3,3'-piperidine] 1-methoxyethyl trimethylsilane

Product 1

HCID 775806586-Chloro-4'-(3-chloro-phenyl)-1'-(3-chloro-propyl)-2'-(2,3-difluoro-6-isopropoxy-phenyl)-2,3-dihydro-2,6'-dioxo spiro[indole-3,3'-piperidine] 1-methoxyethyl trimethylsilane

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a manner similar to the method described in example 24c, racemic (2′S,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-(2,3-difluoro-6-isopropoxy-phenyl)-2,3-dihydro-2,6′-dioxospiro[indole-3,3′-piperidine]-1-methoxyethyl trimethylsilane (1.8 g, 2.72 mmol) prepared in example 73a was reacted with LiH (1.0 g, 125 mmol) and 1-chloro-3-iodo-propane (5.0 g, 24.5 mmol) in N,N-dimethyl-formamide (40 mL) to give racemic (2′R,3R,4′S)-6-chloro-4′-(3-chloro-phenyl)-1′-(3-chloro-propyl)-2′-(2,3-difluoro-6-isopropoxy-phenyl)-2,3-dihydro-2,6′-dioxospiro[indole-3,3′-piperidine]-1-methoxyethyl trimethylsilane as a white form (Yield: 0.67 g, 33.5%).

Sources & evidence

ORD record
ord-8fc78248894248aca85ea1787a0b9111
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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