Hydrochloric Acid → 7-[3-[[(2,3-Dihydro-6,8-dimethoxy-1,4-benzodioxin-2-yl)methyl]amino]propoxy]-2H-1-benzopyran-2-one

HRID 374225Notes

Reaction equation

HRID 374225 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:15]=[C:14]([O:16][CH3:17])[C:7]2[O:8][CH:9]([CH2:12][NH2:13])[CH2:10][O:11][C:6]=2[CH:5]=1.Br[CH2:19][CH2:20][CH2:21][O:22][C:23]1[CH:32]=[C:31]2[C:26]([CH:27]=[CH:28][C:29](=[O:33])[O:30]2)=[CH:25][CH:24]=1.C(N(C(C)C)CC)(C)C.Cl>CN(C=O)C.CO.C(O)(C)C>[CH3:2][O:3][C:4]1[CH:15]=[C:14]([O:16][CH3:17])[C:7]2[O:8][CH:9]([CH2:12][NH:13][CH2:19][CH2:20][CH2:21][O:22][C:23]3[CH:24]=[CH:25][C:26]4[CH:27]=[CH:28][C:29](=[O:33])[O:30][C:31]=4[CH:32]=3)[CH2:10][O:11][C:6]=2[CH:5]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 27571767-(3-bromopropoxy)-2H-chromen-2-oneHCID 197786852,3-Dihydro-6,8-dimethoxy-1,4-benzodioxin-2-methanamine hydrochloride

Product 1

HCID 198095337-[3-[[(2,3-Dihydro-6,8-dimethoxy-1,4-benzodioxin-2-yl)methyl]amino]propoxy]-2H-1-benzopyran-2-one

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3776IsopropanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
96 °C

Procedure

2,3-Dihydro-6,8-dimethoxy-1,4-benzodioxin-2-methanamine hydrochloride (3.58 g, 13.7 mmole), 7-(3-bromopropoxy)coumarin (3.35 g, 11.8 mmole), and diisopropylethylamine (3.25 ml, 18.7 mmole) were combined in 200 ml of DMF and heated at 96° 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, dried over magnesium sulfate, filtered and concentrated in vacuum. The residue was column chromatographed on 300 g of silica gel using first dichloromethane and then 1% methanol/dichloromethane as eluant. The product-containing fractions were combined and concentrated in vacuum and the free base thus obtained redissolved in methanol and 7 ml of 4N isopropanolic HCl added. The mixture was brought to a boil on a hot plate and the solvent gradually replaced with isopropanol. Upon cooling, 0.87 g of the title compound (m.p. 184°-187° C.) precipitated as a white solid, monohydrochloride.

Workup

  1. customThe solvent was then removed
  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 dichloromethane
  7. concentrationconcentrated in vacuum
  8. customthe free base thus obtained
  9. temperatureUpon cooling
  10. custom0.87 g of the title compound (m.p. 184°-187° C.) precipitated as a white solid, monohydrochloride

Sources & evidence

ORD record
ord-e7e4ad2730ce4a78ac216ebcda1a11aa
Source dataset
uspto-grants-1992_11
Patent number
US05166367

Reaction notes

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