Reaktion #43786

Reaktionsgleichung

H2O

6,7-dimethoxyquinolin-4(1H)-one

Cs2CO3

3,4-difluoronitrobenzene

→

product

Ausbeute 47.0%

4-(2-Fluoro-4-nitrophenoxy)-6,7-dimethoxyquinoline

Ausbeute 47.0%

Lösungsmittel

CHCl3

EtOAc

DMF

CH3CN

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe reaction mixture was stirred over the weekend at rt
2. 2
   workup.STIRRINGstirred for 10 minutes
3. 3
   Filtrationthe precipitate was filtered
4. 4
   Waschenwashed with a small amount of H2O
5. 5
   Sonstigeto obtain the 1st crop of solid
6. 6
   Sonstigethe EtOAc layer was separated
7. 7
   Waschenthe aqueous layer was washed with EtOAc (200 mL)
8. 8
   Trocknenthe combined EtOAc solution was dried over MgSO4
9. 9
   Einengenconcentrated in vacuo
10. 10
    Sonstigeto obtain the 2nd crop of solid
11. 11
    workup.ADDITIONa mixture of O- and N-alkylation products
12. 12
    workup.ADDITIONThe mixture of solid product
13. 13
    FiltrationDMF (5 mL), and the undissolved solid was filtered which

Vorschrift

A mixture of 6,7-dimethoxyquinolin-4(1H)-one (7.9 g, 38.5 mmol), Cs2CO3 (15.4 g) in DMF (55 mL) and CH3CN (80 mL) was stirred for 30 min. at rt. To this mixture was added 3,4-difluoronitrobenzene (6.5 g, 40.9 mmol), and the reaction mixture was stirred over the weekend at rt. To the reaction mixture was added H2O (100 mL), stirred for 10 minutes and the precipitate was filtered, washed with a small amount of H2O to obtain the 1st crop of solid. To the filtrate solution was added EtOAc (200 mL), the EtOAc layer was separated, the aqueous layer was washed with EtOAc (200 mL), and the combined EtOAc solution was dried over MgSO4, concentrated in vacuo to obtain the 2nd crop of solid. The solids of first crop and second crop were combined which was a mixture of O- and N-alkylation products. The mixture of solid product was digested in CHCl3 (35 mL) and DMF (5 mL), and the undissolved solid was filtered which was an N-alkylation product. The filtrate solution was passed through a flash column on SiO2 eluting with 5% MeOH in CH2Cl2 to obtain the desired O-alkylation product (6.2 g, 47%) as a light yellow solid. 1H NMR (CDCl3) δ 8.59 (d, 1H, J=5.0 Hz), 8.19 (dd, 1H, J=9.3, 2.8 Hz), 8.14 (dd, 1H, J=8.8, 2.2 Hz), 7.45 (d, 2H, J=9.9 Hz), 7.34 (t, 1H, J=8.3 Hz), 6.55 (d, 1H, J=5.0 Hz), 4.06 (s, 3H), 4.04 (s, 3H).

Quelle