Ethyl Acetate → 5-bromo-3-(4-fluoro-1H-indol-2-yl)pyridin-2-yl trifluoromethanesulfonate

HRID 595679Notes

Reaction equation

HRID 595679 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[NH:10][C:11]3[C:16]([CH:17]=2)=[C:15]([F:18])[CH:14]=[CH:13][CH:12]=3)[C:5]([OH:8])=[N:6][CH:7]=1.CCN(C(C)C)C(C)C.[O:28](S(C(F)(F)F)(=O)=O)[S:29]([C:32]([F:35])([F:34])[F:33])(=O)=[O:30].CC(=O)OCC>CN(C1C=CN=CC=1)C.C(Cl)Cl.O>[F:33][C:32]([F:35])([F:34])[S:29]([O:8][C:5]1[C:4]([C:9]2[NH:10][C:11]3[C:16]([CH:17]=2)=[C:15]([F:18])[CH:14]=[CH:13][CH:12]=3)=[CH:3][C:2]([Br:1])=[CH:7][N:6]=1)(=[O:30])=[O:28]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 178517589HCID 178517589, compound

Product 1

HCID 903338395-bromo-3-(4-fluoro-1H-indol-2-yl)pyridin-2-yl trifluoromethanesulfonateYield 69.8%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 5-bromo-3-(4-fluoro-1H-indol-2-yl)pyridin-2-ol (1.0 g, 3.26 mmol), DIPEA (1.26 g, 9.77 mmol) and DMAP (80 mg, 0.65 mmol) in 15 mL of DCM was added Tf2O (1.84 g, 6.51 mmol) at 0 dropwise. After stirring at room temperature for 3 hours, the mixture was suspended in water and extracted with DCM. Then the combined organic phase was washed with brine, dried over sodium sulfate and concentrated. After column chromatography (PE:EA=20:1), 5-bromo-3-(4-fluoro-1H-indol-2-yl)pyridin-2-yl trifluoromethanesulfonate (1.0 g, yield: 52%) was obtained. 1H-NMR (DMSO-d6, 400 MHz) δ 12.28 (s, 1H), 8.81 (s, 1H), 8.60 (s, 1H), 7.32 (d, J=8.40 Hz, 1H), 7.18˜7.22 (m, 1H), 7.05 (s, 1H), 6.84˜6.87 (m, 1H). MS (M+H)+: 439/441.

Workup

  1. extractionextracted with DCM
  2. washThen the combined organic phase was washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-a1b829b5ffdc409c99f0281d158ddc1f
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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