Cesium carbonate → 4-(2-Fluoro-4-nitrophenoxy)-6,7-dimethoxyquinoline

HRID 1465180Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[OH:15].[F:16][C:17]1[CH:18]=[C:19]([N+:24]([O-:26])=[O:25])[CH:20]=[CH:21][C:22]=1F.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[F:16][C:17]1[CH:18]=[C:19]([N+:24]([O-:26])=[O:25])[CH:20]=[CH:21][C:22]=1[O:15][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][CH:7]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 6,7-dimethoxyquinolin-4-ol (1.4 g, 6.8 mmol, 1.0 eq.), 3,4-difluoro-nitrobenzene (1.44 g, 8.84 mmol, 1.3 eq.) and cesium carbonate (3.6 g, 10.9 mmol, 1.6 eq.) in dry DMF (10 mL) was heated for 1 h at 50° C. in a microwave oven. After cooling to RT the mixture was diluted with water and extracted with EtOAc. The combined organic phase was dried over Na2SO4 and evaporated in vacuo. The crude product was purified by flash chromatography on silica gel (DCM/MeOH=100:0 to 5:1) to yield the desired product A1 (909 mg, 2.64 mmol, 38.8%) as a yellow solid. 1H NMR (400 MHz, CDCl3, 300K) δ 4.04 (s, 3H), 4.06 (s, 3H), 6.55 (d, J=5.2 Hz, 1H), 7.34 (dd, J=7.8 Hz, J=8.8 Hz, 1H), 7.44 (s, 1H), 7.46 (s, 1H), 8.13 (m, 1H), 8.19 (dd, J=9.8 Hz, J=2.5 Hz, 1H), 8.58 (d, J=5.2 Hz, 1H). MS (ES) C17H13FN2O5 requires: 344, found: 345 (M+H)+. Furthermore an isomer (941 mg, 2.74 mmol, 40.2%) was isolated as a yellow solid. MS (ES) C17H13FN2O6 requires: 344. Found: 345 (M+H)+.

Workup

temperatureAfter cooling to RT the mixture
extractionextracted with EtOAc
dry with materialThe combined organic phase was dried over Na2SO4
customevaporated in vacuo
customThe crude product was purified by flash chromatography on silica gel (DCM/MeOH=100:0 to 5:1)

Sources & evidence

ORD record: ord-3a1c24d5de51455991ec2d57a61fbaf9
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08999982B2

Reaction notes

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