4-Aminophenol → 4-[(2-Phenylfuro[3,2-b]pyridin-7-yl)oxy]aniline

HRID 1470353Notes

Reaction equation

Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[O:10][C:3]=12.[NH2:17][C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[C:11]1([C:9]2[O:10][C:3]3[C:4](=[N:5][CH:6]=[CH:7][C:2]=3[O:24][C:21]3[CH:22]=[CH:23][C:18]([NH2:17])=[CH:19][CH:20]=3)[CH:8]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

Conditions

Temperature: 125 °C

Procedure

To a 10 mL sealed tube with stirbar was added 7-chloro-2-phenylfuro[3,2-b]pyridine (300.00 mg; 1.31 mmol; 1.00 eq.), 4-aminophenol (285.09 mg; 2.61 mmol; 2.00 eq.), and caesium carbonate (1 702.45 mg; 5.22 mmol; 4.00 eq.). The mixture was suspended in DMF (7.00 ml) and stirred at 125° C. overnight. The reaction mixture was cooled to room temperature and poured into 150 mL water. Filtered to collect precipitate, washing with water and hexane. The resulting crude material was purified by Biotage chromatography using a KP-NH column (10-50% EtOAc/Hex) to afford the title compound as a beige solid (216 mg, 55%). (HPLC (method F): 99%, RT: 4.73 min); 1H NMR (400 MHz, DMSO-d6) δ [ppm] 8.29 (d, J=5.5, 1H), 7.96 (d, J=7.2, 2H), 7.66 (s, 1H), 7.54 (t, J=7.4, 3H), 7.47 (t, J=7.3, 1H), 6.99 (d, J=8.7, 2H), 6.67 (d, J=8.7, 2H), 6.56 (d, J=5.5, 1H), 5.20 (s, 2H); MS (m/z) 303 [M+H]+, RT: 2.6 min.

Workup

customTo a 10 mL sealed tube with stirbar
temperatureThe reaction mixture was cooled to room temperature
filtrationFiltered
customto collect precipitate
washwashing with water and hexane
customThe resulting crude material was purified by Biotage chromatography

Sources & evidence

ORD record: ord-a3fe20f9e0b949a3a184c4d8e643fdba
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09006440B2

Reaction notes

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