Reacción #461394

Ecuación de reacción

2,3-Dihydro-7-hydroxy-1,4-benzodioxin-2-methanamine

HCl IPA

diisopropylethylamine

sodium iodide

7-(3-chloropropoxy)coumarin

→

beige solid

Rendimiento 16.0%

7-[3-[[(2,3-Dihydro-7-hydroxy-1,4-benzodioxin-2-yl)methyl]amino]propoxy]-2H-1-benzopyran-2-one

Rendimiento 16.0%

Disolventes

DMF

methanol

isopropanol

methanol

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturaheated at 80°-100° C. for 2 days under a nitrogen atmosphere
2. 2
   OtroThe solvent was then removed
3. 3
   LavadoThe mixture was washed with an equal volume of saturated aqueous sodium bicarbonate, with saturated aqueous sodium chloride
4. 4
   Secadodried over magnesium sulfate
5. 5
   Filtraciónfiltered
6. 6
   Concentraciónconcentrated in vacuum
7. 7
   Otrochromatographed on silica gel using first dichloromethane
8. 8
   Concentraciónconcentrated in vacuum
9. 9
   Otrothe pure free base (1.0 g, an additional 2.0 g were obtained of lower purity)
10. 10
    Filtraciónthe title compound was collected by filtration
11. 11
    Otrodried in vacuum at 80° C

Procedimiento

2,3-Dihydro-7-hydroxy-1,4-benzodioxin-2-methanamine (3.00 g, 16.6 mmole), 7-(3-chloropropoxy)coumarin (2.95 g, 12.4 mmole), diisopropylethylamine (8.0 ml, 46.0 mmole) and sodium iodide (2.58 g, 17.2 mmole) were combined in 150 ml of DMF and heated at 80°-100° C. for 2 days under a nitrogen atmosphere. The solvent was then removed and replaced with dichloromethane. The mixture was washed with an equal volume of saturated aqueous sodium bicarbonate, with saturated aqueous sodium chloride, dried over magnesium sulfate, filtered, and concentrated in vacuum. The residue was column chromatographed on silica gel using first dichloromethane and then 0.25% methanol/dichloromethane as eluant. The product-containing fractions were combined and concentrated in vacuum and the pure free base (1.0 g, an additional 2.0 g were obtained of lower purity) redissolved in methanol and boiled on a hot plate, the methanol gradually being replaced with isopropanol. 4N HCl/IPA was added and the title compound was collected by filtration and dried in vacuum at 80° C. The procedure yielded 0.76 g of beige solid, monohydrochloride, m.p. 252° C. (d).

Fuente