2-Fluoro-4-nitrophenol → Methyl 7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridine-2-carboxylate

HRID 500763Notes

Reaction equation

Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[S:10][C:3]=12.[F:15][C:16]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:17]=1[OH:25].C([O-])([O-])=O.[K+].[K+]>O(C1C=CC=CC=1)C1C=CC=CC=1.CCOC(C)=O>[F:15][C:16]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:17]=1[O:25][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[S:10][C:3]=12

Participants

Conditions

Temperature: 180 °C

Procedure

A mixture of 37 (4.0 g, 17.6 mmol), 2-fluoro-4-nitrophenol (5.5 g, 35.0 mmol) and K2CO3 (12.1 g, 87.5 mmol) in Ph2O was heated at 180° C. for 5 hours. The mixture was cooled to room temperature, diluted with EtOAc and washed with water. The organic phase was collected, dried over anhydrous sodium sulfate and the solvents were removed under reduced pressure. The residue was purified by flash chromatography using hexane—AcOEt (70:30) as an eluent. The product from the column was re-crystallized from a mixture of ethyl acetate-hexanes to afford 38 (3.6 g, 59% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ(ppm): 8.69 (d, J=5.2 Hz, 1H), 8.47 (dd, J=2.4 and 10.0 Hz, 1H), 8.27 (s, 1H), 7.77 (dd, J=8.0 and 9.2 Hz, 1H), 7.06 (dd, J=0.8 and 5.2 Hz, 1H), 3.93 (s, 3H).

Workup

temperatureThe mixture was cooled to room temperature
washwashed with water
customThe organic phase was collected
dry with materialdried over anhydrous sodium sulfate
customthe solvents were removed under reduced pressure
customThe residue was purified by flash chromatography
customThe product from the column was re-crystallized from a mixture of ethyl acetate-hexanes

Sources & evidence

ORD record: ord-24d4670dd2874471ab5ae527c5809161
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772247B2

Reaction notes

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