Reacción #61357

Ecuación de reacción

ethyl benzoylacetate

m-anisidine

HCl dioxane

ester c

→

4-hydroxy-2-phenyl-7-methoxyquinoline

Disolventes

toluene

Condiciones de reacción

Tratamiento posterior

1. 1
   LavadoThe cooled toluene solution was successively washed with aqueous 10% HCl (2×300 mL), 1 N NaOH (2×300 mL), H2O (300 mL) and brine (150 mL)
2. 2
   SecadoThe toluene phase was dried (MgSO4)
3. 3
   Filtraciónfiltered
4. 4
   Concentraciónconcentrated under reduced pressure
5. 5
   Otroto give
6. 6
   workup.DISTILLATIONwhile distilling
7. 7
   OtroThe cooled dark solid obtained
8. 8
   Otrowas triturated with CH2Cl2 (200 mL)
9. 9
   FiltraciónThe suspension was filtered
10. 10
    Lavadothe resulting solid washed with CH2Cl2
11. 11
    Otroto give e (22.6 g, 17% from a) as a beige solid

Procedimiento

A solution of ethyl benzoylacetate (b) (100.0 g, 0.52 mol), m-anisidine (a) (128.1 g, 1.04 mol) and 4 N HCl/dioxane (5.2 mL) in toluene (1.0 L) was refluxed for 6.25 h in a Dean-Stark apparatus. The cooled toluene solution was successively washed with aqueous 10% HCl (2×300 mL), 1 N NaOH (2×300 mL), H2O (300 mL) and brine (150 mL). The toluene phase was dried (MgSO4), filtered and concentrated under reduced pressure to give a 1.2:1.0 mixture of ester c and amide d (144.6 g, 45%/38% crude yield) as a dark brown oil. The crude oil was heated to 280° C. for 80 min while distilling generated EtOH. The cooled dark solid obtained was triturated with CH2Cl2 (200 mL). The suspension was filtered and the resulting solid washed with CH2Cl2 to give e (22.6 g, 17% from a) as a beige solid: 1H NMR (DMSO-d6) δ 8.00 (d, J=9.0 Hz, 1H), 7.81-7.82 (m, 2H), 7.57-7.59 (m, 3H), 7.20 (d, J=2.2 Hz, 1H), 6.94 (dd, J=9.0, 2.2 Hz, 1H), 6.26 (s, 1H), 3.87 (s, 3H).

Fuente