Réaction #3196

Équation de réaction

potassium t-butoxide

methyl 2-amino-4-chlorobenzoate

dimethyl acetylenedicarboxylate

dimethyl acetylenedicarboxylate

→

dimethyl 7-chloro-4-hydroxyquinoline-2,3-dicarboxylate

Rendement 28.9%

Solvants

t-butanol

Conditions de réaction

Traitement

1. 1
   Températurewas refluxed for 7 hr under a nitrogen atmosphere
2. 2
   Températurerefluxing another 2.5 hr
3. 3
   AutreA precipitate formed
4. 4
   Températurethe resulting mixture was refluxed for 1.5 hr
5. 5
   TempératureThe mixture was cooled to room temperature
6. 6
   Filtrationfiltered
7. 7
   Autreto separate the solids, which
8. 8
   Lavagewere washed with t-butanol and ether
9. 9
   workup.DISSOLUTIONThe solids were dissolved in water
10. 10
    Autreto form a precipitate
11. 11
    ExtractionThe resulting mixture was extracted with methylene chloride
12. 12
    Lavagethe combined extracts were washed with brine and water
13. 13
    Séchagedried (MgSO4)
14. 14
    Filtrationfiltered
15. 15
    Concentrationconcentrated
16. 16
    Autreto give a green solid
17. 17
    AutreRecrystallization of this material from methanol

Mode opératoire

A stirred mixture of methyl 2-amino-4-chlorobenzoate (2.50 g, 13.5 mM) and dimethyl acetylenedicarboxylate (2.05 g, 14.4 mM) in t-butanol (22 mL) was refluxed for 7 hr under a nitrogen atmosphere. After adding additional dimethyl acetylenedicarboxylate (1.16 g, 8.13 mM) and refluxing another 2.5 hr, the reaction mixture was allowed to cool to room temperature and potassium t-butoxide (1.56 g, 13.9 mM) was added in one portion. A precipitate formed and the resulting mixture was refluxed for 1.5 hr. The mixture was cooled to room temperature and filtered to separate the solids, which were washed with t-butanol and ether. The solids were dissolved in water and acidified with 1N sulfuric acid to form a precipitate. The resulting mixture was extracted with methylene chloride and the combined extracts were washed with brine and water, dried (MgSO4), filtered and concentrated to give a green solid. Recrystallization of this material from methanol provided dimethyl 7-chloro-4-hydroxyquinoline-2,3-dicarboxylate (1.15 g, 28.9%) as an off-white solid, mp 232-233° C.; MS(CI): 296 (M+H).

Source