반응 #43786

반응 방정식

H2O

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

Cs2CO3

3,4-difluoronitrobenzene

→

product

수율 47.0%

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

수율 47.0%

용매

CHCl3

EtOAc

DMF

CH3CN

반응 조건

후처리

1. 1
   workup.STIRRINGthe reaction mixture was stirred over the weekend at rt
2. 2
   workup.STIRRINGstirred for 10 minutes
3. 3
   여과the precipitate was filtered
4. 4
   세척washed with a small amount of H2O
5. 5
   기타to obtain the 1st crop of solid
6. 6
   기타the EtOAc layer was separated
7. 7
   세척the aqueous layer was washed with EtOAc (200 mL)
8. 8
   건조the combined EtOAc solution was dried over MgSO4
9. 9
   농축concentrated in vacuo
10. 10
    기타to 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
    여과DMF (5 mL), and the undissolved solid was filtered which

실험 절차

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).

출처