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

HRID 2082472Notes

Reaction equation

HRID 2082472 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:5]=[CH:6][C:7]2[O:12][CH2:11][C@H:10]([CH2:13][NH2:14])[O:9][C:8]=2[CH:15]=1.Br[CH2:17][CH2:18][CH2:19][O:20][C:21]1[CH:30]=[C:29]2[C:24]([CH:25]=[CH:26][C:27](=[O:31])[O:28]2)=[CH:23][CH:22]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH3:2][O:3][C:4]1[CH:5]=[CH:6][C:7]2[O:12][CH2:11][C@H:10]([CH2:13][NH:14][CH2:17][CH2:18][CH2:19][O:20][C:21]3[CH:22]=[CH:23][C:24]4[CH:25]=[CH:26][C:27](=[O:31])[O:28][C:29]=4[CH:30]=3)[O:9][C:8]=2[CH:15]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27571767-(3-bromopropoxy)-2H-chromen-2-oneHCID 70200787(S)-7-methoxy-2,3-dihydro-1,4-benzodioxin-2-methanamine hydrochloride

Product 1

HCID 54129617(S)-7-[3-[[(2,3-Dihydro-7-methoxy-1,4-benzodioxin-2-yl)methyl]amino]propoxy]-2H-1-benzopyran-2-oneYield 30.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

(S)-2,3-Dihydro-7-methoxy-1,4-benzodioxin-2-methanamine hydrochloride (11.5 g, 49.8 mmole), 7-(3-bromopropoxy)coumarin (14.2 g, 50.0 mmole), and diisopropylethylamine (12 ml, 68.9 mmole) were combined in 350 ml of DMF and heated at 90° C. for 24 hours under a nitrogen atmosphere. The solvent was then removed in vacuum and replaced with 300 ml of dichloromethane. Upon addition of an equal volume of saturated aqueous sodium bicarbonate, a white solid precipitated. This was filtered and redissolved in 550 ml of warm methanol and 35 ml of 4N isopropanolic HCl was added. The solution was boiled on a hot plate and the solvent gradually replaced with isopropanol. Upon cooling, 0.54 g of the title compound precipitated as a white solid, monohydrochloride, quarter hydrate, m.p. 225°-227° C. Subsequent crops yielded as additional 6.1 g of product.

Workup

  1. customThe solvent was then removed in vacuum
  2. additionUpon addition of an equal volume of saturated aqueous sodium bicarbonate
  3. customa white solid precipitated
  4. filtrationThis was filtered
  5. dissolutionredissolved in 550 ml of warm methanol
  6. addition35 ml of 4N isopropanolic HCl was added
  7. temperatureUpon cooling
  8. custom0.54 g of the title compound precipitated as a white solid, monohydrochloride, quarter hydrate, m.p. 225°-227° C

Sources & evidence

ORD record
ord-dffb9ebe8de6498ebf15e0bd11f3ac83
Source dataset
uspto-grants-1993_02
Patent number
US05189171

Reaction notes

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