Реакция #3196

Уравнение реакции

potassium t-butoxide

methyl 2-amino-4-chlorobenzoate

dimethyl acetylenedicarboxylate

dimethyl acetylenedicarboxylate

→

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

Выход 28.9%

Растворители

t-butanol

Условия реакции

Обработка

1. 1
   Температураwas refluxed for 7 hr under a nitrogen atmosphere
2. 2
   Температураrefluxing another 2.5 hr
3. 3
   ДругоеA precipitate formed
4. 4
   Температураthe resulting mixture was refluxed for 1.5 hr
5. 5
   ТемператураThe mixture was cooled to room temperature
6. 6
   Фильтрацияfiltered
7. 7
   Другоеto separate the solids, which
8. 8
   Промывкаwere washed with t-butanol and ether
9. 9
   workup.DISSOLUTIONThe solids were dissolved in water
10. 10
    Другоеto form a precipitate
11. 11
    ЭкстракцияThe resulting mixture was extracted with methylene chloride
12. 12
    Промывкаthe combined extracts were washed with brine and water
13. 13
    Сушкаdried (MgSO4)
14. 14
    Фильтрацияfiltered
15. 15
    Концентрированиеconcentrated
16. 16
    Другоеto give a green solid
17. 17
    ДругоеRecrystallization of this material from methanol

Методика

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).

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