Diisopropylethylamine → 7-[3-[(7-Hydroxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)amino]propoxy]chromen-4-one

HRID 5573

Reaction equation

HRID 5573 reaction equation
Cl.[OH:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH2:10][CH:9]([CH2:12][NH2:13])[O:8][C:7]=2[CH:14]=1.Br[CH2:16][CH2:17][CH2:18][O:19][C:20]1[CH:29]=[C:28]2[C:23]([C:24](=[O:30])[CH:25]=[CH:26][O:27]2)=[CH:22][CH:21]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[OH:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH2:10][CH:9]([CH2:12][NH:13][CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:29]=[C:28]4[C:23]([C:24](=[O:30])[CH:25]=[CH:26][O:27]4)=[CH:22][CH:21]=3)[O:8][C:7]=2[CH:14]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 189238902,3-Dihydro-7-hydroxy-1,4-benzodioxin-2-methanamine hydrochlorideHCID 197967547-(3-Bromopropoxy)chromen-4-one

Product 1

HCID 197967627-[3-[(7-Hydroxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)amino]propoxy]chromen-4-oneYield 10.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

2,3-Dihydro-7-hydroxy-1,4-benzodioxin-2-methanamine hydrochloride (4.7 g, 22 mmole), 7-(3-bromopropoxy)chromen-4-one (6.1 g, 22 mmole) and diisopropylethylamine (18.8 ml, 108 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 and replaced with dichloromethane. The mixture was washed with an equal volume of saturated aqueous sodium bicarbonate, with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuum. The residue was chromatographed on a silica gel column using first dichloromethane and then 5% methanol/dichloromethane as eluents. The fractions containing material with Rf=0.37 on silica gel tlc (chloroform/methanol/ammonia=95/5/1) were combined, concentrated, and the residual solid was recrystallized from ethanol with the addition of 4N isopropanolic HCl and ether to give 0.85 g of title compound as a light brown solid hydrochloride, quarter hydrate, m.p. 186°-189° C.

Workup

  1. customThe solvent was then removed
  2. washThe mixture was washed with an equal volume of saturated aqueous sodium bicarbonate, with saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuum
  6. customThe residue was chromatographed on a silica gel column
  7. additionThe fractions containing material with Rf=0.37 on silica gel tlc (chloroform/methanol/ammonia=95/5/1)
  8. concentrationconcentrated
  9. customthe residual solid was recrystallized from ethanol with the addition of 4N isopropanolic HCl and ether

Sources & evidence

ORD record
ord-b5f1118b8c30426bbd0a88c29f75d946
Source dataset
uspto-grants-1993_09
Patent number
US05245051

Linked notes

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