Réaction #61357

Équation de réaction

ethyl benzoylacetate

m-anisidine

HCl dioxane

ester c

→

4-hydroxy-2-phenyl-7-methoxyquinoline

Solvants

toluene

Conditions de réaction

Traitement

1. 1
   LavageThe 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
   SéchageThe toluene phase was dried (MgSO4)
3. 3
   Filtrationfiltered
4. 4
   Concentrationconcentrated under reduced pressure
5. 5
   Autreto give
6. 6
   workup.DISTILLATIONwhile distilling
7. 7
   AutreThe cooled dark solid obtained
8. 8
   Autrewas triturated with CH2Cl2 (200 mL)
9. 9
   FiltrationThe suspension was filtered
10. 10
    Lavagethe resulting solid washed with CH2Cl2
11. 11
    Autreto give e (22.6 g, 17% from a) as a beige solid

Mode opératoire

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).

Source