Reacción #3196

Ecuación de reacción

potassium t-butoxide

methyl 2-amino-4-chlorobenzoate

dimethyl acetylenedicarboxylate

dimethyl acetylenedicarboxylate

→

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

Rendimiento 28.9%

Disolventes

t-butanol

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturawas refluxed for 7 hr under a nitrogen atmosphere
2. 2
   Temperaturarefluxing another 2.5 hr
3. 3
   OtroA precipitate formed
4. 4
   Temperaturathe resulting mixture was refluxed for 1.5 hr
5. 5
   TemperaturaThe mixture was cooled to room temperature
6. 6
   Filtraciónfiltered
7. 7
   Otroto separate the solids, which
8. 8
   Lavadowere washed with t-butanol and ether
9. 9
   workup.DISSOLUTIONThe solids were dissolved in water
10. 10
    Otroto form a precipitate
11. 11
    ExtracciónThe resulting mixture was extracted with methylene chloride
12. 12
    Lavadothe combined extracts were washed with brine and water
13. 13
    Secadodried (MgSO4)
14. 14
    Filtraciónfiltered
15. 15
    Concentraciónconcentrated
16. 16
    Otroto give a green solid
17. 17
    OtroRecrystallization of this material from methanol

Procedimiento

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).

Fuente