Ethyl Acetate → 2-(5-bromo-2-vinylpyridin-3-yl)-4-fluoro-1H-indole

HRID 595680Notes

Reaction equation

FC(F)(F)S(O[C:7]1[C:12]([C:13]2[NH:14][C:15]3[C:20]([CH:21]=2)=[C:19]([F:22])[CH:18]=[CH:17][CH:16]=3)=[CH:11][C:10]([Br:23])=[CH:9][N:8]=1)(=O)=O.[CH2:26]([Sn](CCCC)(CCCC)C=C)[CH2:27]CC.[Li+].[Cl-].CC(=O)OCC>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:23][C:10]1[CH:11]=[C:12]([C:13]2[NH:14][C:15]3[C:20]([CH:21]=2)=[C:19]([F:22])[CH:18]=[CH:17][CH:16]=3)[C:7]([CH:26]=[CH2:27])=[N:8][CH:9]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 5-bromo-3-(4-fluoro-1H-indol-2-yl)pyridin-2-yl trifluoromethanesulfonate (700 mg, 1.59 mmol), tributyl(vinyl)stannane (556 mg, 1.75 mmol), LiCl (202 mg, 4.78 mmol) and Pd(PPh3)2Cl2 (100 mg) in DMF (20 mL) was stirred at 60° C. for 3 hours under nitrogen atmosphere. The mixture was filtered through celite and concentrated in vacuo to remove DMF, and then the residue was suspended in water/EA. After extracted with EA, the combined organic phase was washed with brine, dried over sodium sulfate and concentrated to afford 2-(5-bromo-2-vinylpyridin-3-yl)-4-fluoro-1H-indole (400 mg, yield: 79%) through the column chromatography (PE:EA=20:1). 1H-NMR (CDCl3, 400 MHz) δ 8.64 (s, 1H), 8.46 (s, 1H), 7.93 (s, 1H), 7.14˜7.22 (m, 2H), 7.00˜7.07 (m, 1H), 6.82˜6.86 (m, 1H), 6.76 (s, 1H), 6.43˜6.47 (m, 1H), 5.54˜5.58 (m, 1H). MS (M+H)+: 317/319.

Workup

filtrationThe mixture was filtered through celite and
concentrationconcentrated in vacuo
customto remove DMF
extractionAfter extracted with EA
washthe combined organic phase was washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated

Sources & evidence

ORD record: ord-0c1ad13d887f4096bedf64f33a50021d
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09243002B2

Reaction notes

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