N-Ethyl-2,3-dihydro-1,4-benzodioxin-2-methanamine → 7-[3-[[(2,3-Dihydro-1,4-benzodioxin-2-yl)methyl]ethylamino]propoxy]-2H-1-benzopyran-2-one

HRID 2082475Notes

Reaction equation

HRID 2082475 reaction equation
[CH2:1]([NH:3][CH2:4][CH:5]1[O:10][C:9]2[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=2[O:7][CH2:6]1)[CH3:2].Br[CH2:16][CH2:17][CH2:18][O:19][C:20]1[CH:29]=[C:28]2[C:23]([CH:24]=[CH:25][C:26](=[O:30])[O:27]2)=[CH:22][CH:21]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[O:10]1[C:9]2[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=2[O:7][CH2:6][CH:5]1[CH2:4][N:3]([CH2:1][CH3:2])[CH2:16][CH2:17][CH2:18][O:19][C:20]1[CH:21]=[CH:22][C:23]2[CH:24]=[CH:25][C:26](=[O:30])[O:27][C:28]=2[CH:29]=1

Participants

5

Reactant 3

HCID 30614N-Ethyl-2,3-dihydro-1,4-benzodioxin-2-methanamineHCID 81531DiisopropylethylamineHCID 27571767-(3-bromopropoxy)-2H-chromen-2-one

Product 1

HCID 197786847-[3-[[(2,3-Dihydro-1,4-benzodioxin-2-yl)methyl]ethylamino]propoxy]-2H-1-benzopyran-2-oneYield 51.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
76 °C

Procedure

N-Ethyl-2,3-dihydro-1,4-benzodioxin-2-methanamine (4.67 g, 24.2 mmole), 7-(3-bromopropoxy)coumarin (6.92 g, 24.4 mmole), and diisopropylethylamine (6.70 ml, 38.5 mmole) were combined in 300 ml of DMF and heated at 76° C. for 24 hours under a nitrogen atmosphere. The solvent was then removed in vacuum and replaced with dichloromethane. The mixture was washed with an equal volume of saturated aqueous sodium bicarbonate, dried over magnesium sulfate, filtered and concentrated in vacuum. The residue (10 g) was column chromatographed on 225 g of silica gel using 40% ethyl acetate/dichloromethane as eluant. The product-containing fractions were concentrated in vacuum and the residue crystallized from isopropanol with the addition of 30 ml of 4N isopropanolic HCl to give 4.94 g of the title compound as a white solid, monohydrochloride, m.p. 147°-152° C.

Workup

  1. customThe solvent was then removed in vacuum
  2. washThe mixture was washed with an equal volume of saturated aqueous sodium bicarbonate
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuum
  6. customchromatographed on 225 g of silica gel using 40% ethyl acetate/dichloromethane as eluant
  7. concentrationThe product-containing fractions were concentrated in vacuum
  8. customthe residue crystallized from isopropanol with the addition of 30 ml of 4N isopropanolic HCl

Sources & evidence

ORD record
ord-7155d65dfa884794ae690469367ca06c
Source dataset
uspto-grants-1993_02
Patent number
US05189171

Reaction notes

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