Trifluoromethanesulfonic anhydride → 6-chloro-2-(5-fluoro-1H-indol-2-yl)pyridin-3-yl trifluoromethanesulfonate

HRID 595657Notes

Reaction equation

HRID 595657 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[NH:9][C:10]3[C:15]([CH:16]=2)=[CH:14][C:13]([F:17])=[CH:12][CH:11]=3)[C:5]([OH:18])=[CH:4][CH:3]=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]>C(Cl)Cl.O>[F:33][C:32]([F:35])([F:34])[S:29]([O:18][C:5]1[C:6]([C:8]2[NH:9][C:10]3[C:15]([CH:16]=2)=[CH:14][C:13]([F:17])=[CH:12][CH:11]=3)=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=1)(=[O:30])=[O:28]

Participants

6

Reactant 3

HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 903334926-chloro-2-(5-fluoro-1H-indol-2-yl)pyridin-3-ol

Product 1

HCID 903336636-chloro-2-(5-fluoro-1H-indol-2-yl)pyridin-3-yl trifluoromethanesulfonateYield 77.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a degassed solution of 6-chloro-2-(5-fluoro-1H-indol-2-yl)pyridin-3-ol (600 mg, 2.28 mmol) and DIPEA (1.0 g, 7.74 mmol) in DCM (10 mL), Tf2O (1.3 g, 4.61 mmol) were added dropwise under N2 at 0° C. The mixture was stirred at RT for 2 hours. The mixture was diluted with water and extracted with DCM. The organic layers were washed with brine, dried over Na2SO4, and concentrated. The mixture was purified by column chromatography (PE:EA=10:1) to give 6-chloro-2-(5-fluoro-1H-indol-2-yl)pyridin-3-yl trifluoromethanesulfonate (700 mg, yield: 77.6%). 1H-NMR (DMSO-d6, 400 MHz) δ 11.91 (br s, 1H), 8.17 (d, J=8.8 Hz, 1H), 7.66 (d, J=8.8 Hz, 1H), 7.51˜7.58 (m, 1H), 7.42˜7.50 (m, 1H), 7.18 (d, J=1.6 Hz, 1H), 7.06˜7.14 (m, 1H). MS (M+H)+: 395/397.

Workup

  1. extractionextracted with DCM
  2. washThe organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe mixture was purified by column chromatography (PE:EA=10:1)

Sources & evidence

ORD record
ord-7531ad19080a4d2ba28a7c6878527b2c
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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