Lithium hydride → racemic (2'S,3S,4'R)-1'-[(tert-butoxycarbonylamino)ethyl]-6-chloro-2'-(3-chlorophenyl)-4'-(5-fluoro-2-methyl-phenyl)-2,3-dihydro-2,6'-dioxo spiro[indole-3,3'-piperidine] 1-methoxyethyl trimethylsilane

HRID 1728085Notes

Reaction equation

HRID 1728085 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+].[C:43]([O:47][C:48](=[O:53])[NH:49][CH2:50][CH2:51]Br)([CH3:46])([CH3:45])[CH3:44]>CN(C)C=O>[C:43]([O:47][C:48]([NH:49][CH2:50][CH2:51][N:12]1[C:13](=[O:24])[CH2:14][CH:15]([C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=2[CH3:23])[C:10]2([C:5]3[C:6](=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[NH:8][C:9]2=[O:32])[CH:11]1[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[CH:26]=1)=[O:53])([CH3:46])([CH3:45])[CH3:44].[CH3:33][O:34][CH:35]([Si:37]([CH3:40])([CH3:39])[CH3:38])[CH3:36]

Participants

5

Reactant 3

HCID 62714Lithium hydrideHCID 4103526tert-Butyl N-(2-bromoethyl)carbamateHCID 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 77580098racemic (2'S,3S,4'R)-1'-[(tert-butoxycarbonylamino)ethyl]-6-chloro-2'-(3-chlorophenyl)-4'-(5-fluoro-2-methyl-phenyl)-2,3-dihydro-2,6'-dioxo spiro[indole-3,3'-piperidine] 1-methoxyethyl trimethylsilaneYield 14.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a manner similar to the method described in example 152a, 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 (0.45 g, 0.75 mmol) was reacted with LiH (0.15 g, 18.8 mmol) and (2-bromo-ethyl)-carbamic acid tert-butyl ester (1.0 g, 4.52 mmol) in N,N-dimethyl-formamide (3 mL), a catalytic amount of KI to give racemic (2′S,3S,4′R)-1′-[(tert-butoxycarbonylamino)ethyl]-6-chloro-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 (80 mg).

Sources & evidence

ORD record
ord-11e234db520148df90abfeda4e35346c
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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