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

HRID 374226Notes

Reaction equation

HRID 374226 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][C@H:8]([CH2:11][NH2:12])[O:7][C:6]=2[CH:13]=1.Br[CH2:15][CH2:16][CH2:17][O:18][C:19]1[CH:28]=[C:27]2[C:22]([CH:23]=[CH:24][C:25](=[O:29])[O:26]2)=[CH:21][CH:20]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][C@H:8]([CH2:11][NH:12][CH2:15][CH2:16][CH2:17][O:18][C:19]3[CH:20]=[CH:21][C:22]4[CH:23]=[CH:24][C:25](=[O:29])[O:26][C:27]=4[CH:28]=3)[O:7][C:6]=2[CH:13]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27571767-(3-bromopropoxy)-2H-chromen-2-oneHCID 22844790(S)-2,3-Dihydro-7-hydroxy-1,4-benzodioxin-2-methanamine

Product 1

HCID 53802521(S)-7-[3-[[(2,3-Dihydro-7-hydroxy-1,4-benzodioxin-2-yl)methyl]amino]propoxy]-2H-1-benzopyran-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
86 °C

Procedure

(S)-2,3-Dihydro-7-hydroxy-1,4-benzodioxin-2-methanamine (3.53 g, 16.2 mmole), 7-(3-bromopropoxy)coumarin (4.17 g, 14.7 mmole), and diisopropylethylamine (5.00 ml, 28.7 mmole) were combined in 300 ml of DMF and heated at 86° 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 was column chromatographed on 300 g of silica gel using first 75% ethyl acetate/dichloromethane and then 2% methanol/dichloromethane as eluant. The product-containing fractions were concentrated in vacuum and the free base redissolved in warm methanol. Five ml of 4N isopropanolic HCl was added, the mixture was brought to a boil on a hot plate and the solvent gradually replaced with isopropanol. Upon cooling, 2.24 g of the title compound precipitated as an white solid, monohydrochloride, m.p. 245°-248° 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 300 g of silica gel using first 75% ethyl acetate/dichloromethane
  7. concentrationThe product-containing fractions were concentrated in vacuum
  8. dissolutionthe free base redissolved in warm methanol
  9. additionFive ml of 4N isopropanolic HCl was added
  10. temperatureUpon cooling
  11. custom2.24 g of the title compound precipitated as an white solid, monohydrochloride, m.p. 245°-248° C.

Sources & evidence

ORD record
ord-00472e70b7ff4bdd848a408128c02df9
Source dataset
uspto-grants-1992_11
Patent number
US05166367

Reaction notes

Loading…