Boron tribromide → 2-(6-Fluoro-5-methylamino-pyridin-2-yl)-benzofuran-5-ol
Reaction equation
[F:1][C:2]1[C:7]([NH:8][CH3:9])=[CH:6][CH:5]=[C:4]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([O:19]C)=[CH:15][C:13]=3[CH:14]=2)[N:3]=1.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>ClCCl>[F:1][C:2]1[N:3]=[C:4]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][C:13]=3[CH:14]=2)[CH:5]=[CH:6][C:7]=1[NH:8][CH3:9]Participants
Procedure
To a stirred solution of [2-fluoro-6-(5-methoxy-benzofuran-2-yl)-pyridin-3-yl]-methyl-amine (31 mg, 0.114 mmol) in dichloromethane (3 mL) at 0° C. under nitrogen atmosphere, BBr3 (1M solution in CH2Cl2, 0.568 mL, 0.568 mmol) was added dropwise. The reaction mixture was stirred for 1.5 hours at room temperature. The mixture was then cooled to 0° C., saturated sodium bicarbonate solution was added (5 mL) and the resulting mixture was extracted with dichloromethane (50 mL). The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. Purification of the crude product by flash chromatography using 30% ethyl acetate in hexane afforded the title compound 2-(6-fluoro-5-methylamino-pyridin-2-yl)-benzofuran-5-ol (22 mg) as an off-white solid. 1H NMR (400 MHz, METHANOL-d4) δ: 7.62 (d, J=7.90 Hz, 1H), 7.28 (d, J=8.78 Hz, 1H), 7.08 (dd, J=10.54, 8.20 Hz, 1H), 6.97 (s, 1H), 6.92 (d, J=2.34 Hz, 1H), 6.74 (dd, J=8.78, 2.34 Hz, 1H), 2.87 (s, 3H). ESMS: m/z 259.47 [M+1]+
Workup
- temperatureThe mixture was then cooled to 0° C.
- extractionthe resulting mixture was extracted with dichloromethane (50 mL)
- washThe organic layer was washed with brine
- dry with materialdried over Na2SO4
- concentrationconcentrated under reduced pressure
- customPurification of the crude product by flash chromatography
Sources & evidence
- ORD record
- ord-70e3c5e4564c419c926405e19fc73faf
- Source dataset
- uspto-grants-2010_08
- Patent number
- US07772256B2
Reaction notes
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