Methanol → 6-Chloro-4'-(3-chlorophenyl)-2'-(5-fluoro-2-methylphenyl)-2,3-dihydro-2,6'-dioxo spiro[indole-3,3'-piperidine] 1-methoxyethyl trimethylsilane

HRID 1728005Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:17])=[C:6]([CH:8]=[N:9][C:10]([O:12][Si:13]([CH3:16])([CH3:15])[CH3:14])=[CH2:11])[CH:7]=1.[Cl:18][C:19]1[CH:27]=[C:26]2[C:22](/[C:23](=[CH:37]/[C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([Cl:44])[CH:39]=3)/[C:24](=[O:36])[N:25]2[CH2:28][O:29][CH2:30][CH2:31][Si](C)(C)C)=[CH:21][CH:20]=1.CO>C1(C)C=CC=CC=1>[Cl:18][C:19]1[CH:27]=[C:26]2[NH:25][C:24](=[O:36])[C:23]3([CH:37]([C:38]4[CH:43]=[CH:42][CH:41]=[C:40]([Cl:44])[CH:39]=4)[CH2:12][C:10](=[O:11])[NH:9][CH:8]3[C:6]3[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[CH3:17])[C:22]2=[CH:21][CH:20]=1.[CH3:28][O:29][CH:30]([Si:13]([CH3:14])([CH3:15])[CH3:16])[CH3:31]

Participants

Conditions

Temperature: 148 °C

Procedure

To a solution of 1-(5-fluoro-2-methylphenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene prepared in example 36a in toluene (50 mL) was added E/Z-6-chloro-3-(3-chloro-benzylidene)-1-(2-trimethylsilanyl-ethoxymethyl)-1,3-dihydro-indole-2-one prepared in example 55a (3.0 g, 7.14 mmol). The reaction mixture was stirred under nitrogen in a sealed tube at 148° C. for 40 min. After the solution was cooled to room temperature, methanol (50 mL) was added, and then the mixture was concentrated. The residue was purified by chromatography (EtOAc:Hexane=2:1) to give racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-(5-fluoro-2-methylphenyl)-2,3-dihydro-2,6′-dioxospiro[indole-3,3′-piperidine]-1-methoxyethyl trimethylsilane as an off-white solid (Yield 2.1 g, 49%).

Workup

temperatureAfter the solution was cooled to room temperature
concentrationthe mixture was concentrated
customThe residue was purified by chromatography (EtOAc:Hexane=2:1)

Sources & evidence

ORD record: ord-b44b54ee04b84d2897555f258223ea10
Source dataset: uspto-grants-2009_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07495007B2

Reaction notes

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