반응 #461404

반응 방정식

(S)-2,3-Dihydro-6,7-methylenedioxy-1,4-benzodioxin-2-methanamine hydrochloride

7-(3-chloropropoxy)coumarin

sodium iodide

→

title compound

수율 16.3%

(S)-7-[3-[[(2,3-Dihydro-6,7-methylenedioxy-1,4-benzodioxin-2-yl)methyl]amino]propoxy]-2H-1-benzopyran-2-one

수율 16.3%

용매

DMF

반응 조건

후처리

1. 1
   기타The solvent was then removed in vacuum
2. 2
   workup.ADDITIONThe mixture was treated with an equal volume of saturated aqueous sodium bicarbonate
3. 3
   추출the aqueous phase was then back-extracted with 3:1 chloroform-isopropanol
4. 4
   세척The combined organic extracts were washed with water
5. 5
   건조dried over anhydrous magnesium sulfate
6. 6
   여과filtered
7. 7
   농축concentrated under vacuum
8. 8
   기타The residue was chromatographed on a silica gel column
9. 9
   농축concentrated in vacuum
10. 10
    workup.DISSOLUTIONthe residue redissolved in methanol
11. 11
    기타acidified with 4N HCl/isopropanol to pH<3 in an ice bath
12. 12
    기타to precipitate a white solid
13. 13
    기타This was recrystallized from methanol
14. 14
    기타triturated with a small amount of isopropanol

실험 절차

(S)-2,3-Dihydro-6,7-methylenedioxy-1,4-benzodioxin-2-methanamine hydrochloride (5.50 g, 22.4 mmole), 7-(3-chloropropoxy)coumarin (5.49 g, 23.0 mmole) diisopropylethylamine (39.0 ml, 224 mmol) and sodium iodide (3.45 g, 23.0 mmole) were combined in 200 ml of DMF and heated at 80° C. for 24 hours under a nitrogen atmosphere. The solvent was then removed in vacuum and replaced with chloroform. The mixture was treated with an equal volume of saturated aqueous sodium bicarbonate and the aqueous phase was then back-extracted with 3:1 chloroform-isopropanol. The combined organic extracts were washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum. The residue was chromatographed on a silica gel column using dichloromethane as eluant. The product-containing fractions (Rf=0.59 on silica gel tlc with 1:5:95 ammonium hydroxide-methanol-chloroform) were combined and concentrated in vacuum, and the residue redissolved in methanol and acidified with 4N HCl/isopropanol to pH<3 in an ice bath to precipitate a white solid. This was recrystallized from methanol and triturated with a small amount of isopropanol to give 1.50 g of the title compound as an off-white crystalline, solid, monohydrochloride, m.p. 244°-245° C.

출처