Potassium Fluoride → 3-[4-(6-Chloro-pyridin-3-yl)-5,5-dimethyl-5h-furan-(2e)-ylidene]-6-fluoro-1,3-dihydro-indol-2-one

HRID 333387Notes

Reaction equation

Br[C:2]1[C:6]([CH3:8])([CH3:7])[O:5]/[C:4](=[C:9]2/[C:10](=[O:19])[NH:11][C:12]3[C:17]/2=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=3)/[CH:3]=1.[F-].[K+].[Cl:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][N:24]=1>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:22][C:23]1[N:24]=[CH:25][C:26]([C:2]2[C:6]([CH3:8])([CH3:7])[O:5]/[C:4](=[C:9]3/[C:10](=[O:19])[NH:11][C:12]4[C:17]/3=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=4)/[CH:3]=2)=[CH:27][CH:28]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of (3E)-3-(4-bromo-5,5-dimethylfuran-2(5H)-ylidene)-6-fluoro-1,3-dihydro-2H-indol-2-one (3.0 g, 9.3 mmol, 1 eq.) in 1,4-dioxane (240 mL) were added Pd(dppf)Cl2 (0.36 g, 0.49 mmol, 0.05 eq.) and 1 M KF aqueous solution (37.5 mL, 37.5 mmol, 4 eq.). The reaction mixture was first heated at 70° C. under Ar and was then added 2-chloro-5-pyridineboronic acid (1.57 g, 10.0 mmol, 1.08 eq.) in several portions in 15 minutes. The reaction mixture was continuously heated at 70° C. under Ar for another 22 hours. LC-MS analysis confirmed that (3E)-3-(4-bromo-5,5-dimethylfuran-2(5H)-ylidene)-6-fluoro-1,3-dihydro-2H-indol-2-one had completely disappeared and 3-[4-(6-chloro-pyridin-3-yl)-5,5-dimethyl-5H-furan-(2E)-ylidene]-6-fluoro-1,3-dihydro-indol-2-one was produced (ESI-MS m/z 357.0 (M+H)+).

Workup

temperatureThe reaction mixture was continuously heated at 70° C. under Ar for another 22 hours

Sources & evidence

ORD record: ord-d898e82c643143308a707fc40c5f5ccc
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08877923B2

Reaction notes

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