1-(3-Fluorophenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene → Racemic (2'S,3S,4'R)-4'-[5-bromo-2-(1-tert-butoxycarbonyl-piperidin-4-yloxy)-phenyl]-6-chloro-2'-(3-fluorophenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 504504Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[N:9][C:10]([O:12][Si](C)(C)C)=[CH2:11])[CH:5]=[CH:6][CH:7]=1.C(OC([N:24]1[C:32]2[C:27](=[CH:28][CH:29]=[C:30]([Cl:33])[CH:31]=2)/[C:26](=[CH:34]/[C:35]2[CH:40]=[C:39]([Br:41])[CH:38]=[CH:37][C:36]=2[O:42][CH:43]2[CH2:48][CH2:47][N:46]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:45][CH2:44]2)/[C:25]1=[O:56])=O)(C)(C)C>C1(C)C=CC=CC=1>[Br:41][C:39]1[CH:38]=[CH:37][C:36]([O:42][CH:43]2[CH2:44][CH2:45][N:46]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:47][CH2:48]2)=[C:35]([CH:34]2[CH2:12][C:10](=[O:11])[NH:9][CH:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)[C:26]32[C:27]2[C:32](=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=2)[NH:24][C:25]3=[O:56])[CH:40]=1

Participants

Conditions

Temperature: 140 °C

Procedure

To a solution of 1-(3-fluoro-phenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene in example 36a (24 mmol) in toluene (100 mL) was added E/Z-3-[5-bromo-2-(1-tert-butoxycarbonyl-piperidin-4-yloxy)-benzylidene]-6-chloro-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester (3.85 g, 6 mmol). The reaction mixture was stirred under argon at 140° C. for 5 h. After cooled to room temperature, the mixture was concentrated. The residue was purified by chromatography (20%-30% EtOAc:DCM) to give the title compound as a off white solid (Yield: 0.38 g).

Workup

temperatureAfter cooled to room temperature
concentrationthe mixture was concentrated
customThe residue was purified by chromatography (20%-30% EtOAc:DCM)

Sources & evidence

ORD record: ord-0b5c76345e3d4891b738d53d34b0fb10
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07776875B2

Reaction notes

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