Hydrochloric Acid → HCID 19891047, compound

HRID 893725Notes

Reaction equation

HRID 893725 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH:8]([CH2:11][NH2:12])[O:7][C:6]=2[C:13]=1[CH3:14].[N+:15]([C:18]1[CH:19]=[C:20]([CH:26]=[CH:27][CH:28]=1)[O:21][CH2:22][CH2:23][CH2:24]Br)([O-])=O.C(N(C(C)C)CC)(C)C.Cl>CN(C=O)C.CO.[Pd]>[NH2:15][C:18]1[CH:19]=[C:20]([CH:26]=[CH:27][CH:28]=1)[O:21][CH2:22][CH2:23][CH2:24][NH:12][CH2:11][CH:8]1[O:7][C:6]2[C:13]([CH3:14])=[C:2]([OH:1])[CH:3]=[CH:4][C:5]=2[O:10][CH2:9]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 71723011-(3-Bromopropoxy)-3-nitrobenzeneHCID 198910552,3-Dihydro-7-hydroxy-8-methyl-1,4-benzodioxin-2-methanamine

Product 1

HCID 19891047HCID 19891047, compoundYield 25.8%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

2,3-Dihydro-7-hydroxy-8-methyl-1,4-benzodioxin-2-methanamine (0.70 g, 3.6 mmole), 3-(3-nitrophenoxy)propyl bromide (0.94 g, 3.6 mmole) and diisopropylethylamine (0.47 g, 3.6 mmole) were combined in 50 ml of DMF and heated at 80° C. for 24 hrs. under a nitrogen atmosphere. The solvent was then removed in vacuum and the residue dissolved in chloroform and washed with saturated aqueous sodium bicarbonate, dried over magnesium sulfate, filtered and concentrated in vacuum. The residue was column chromatographed on silica gel using first chloroform and then 2% methanol/chloroform as eluant. The product-containing fractions were combined and concentrated in vacuum to give a dark yellow oil. This was dissolved in methanol (100 ml) and 0.5 g of 10% palladium on carbon added, along with 5 ml of 4N isopropanolic HCl. The mixture was hydrogenated at 50 psi on a Parr apparatus overnight, filtered through celite, concentrated in vacuum. to an off-white solid and column chromatographed on silica gel with 5% methanol/chloroform (with 1 ml/liter aqueous ammonia added). The product-containing fractions were combined and evaporated in vacuum and recrystallized from isopropanol with addition of 4N HCl/IPA to give 0.32 g of title compound as a yellow solid, dihydrochloride, hydrate, isopropanol solvate, m.p. 156° C. (d).

Workup

  1. customThe solvent was then removed in vacuum
  2. dissolutionthe residue dissolved in chloroform
  3. washwashed with saturated aqueous sodium bicarbonate
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuum
  7. customchromatographed on silica gel using first chloroform
  8. concentrationconcentrated in vacuum
  9. customto give a dark yellow oil
  10. customwas hydrogenated at 50 psi on a Parr apparatus overnight
  11. filtrationfiltered through celite
  12. concentrationconcentrated in vacuum
  13. customto an off-white solid and column chromatographed on silica gel with 5% methanol/chloroform (with 1 ml/liter aqueous ammonia added)
  14. customevaporated in vacuum
  15. customrecrystallized from isopropanol with addition of 4N HCl/IPA

Sources & evidence

ORD record
ord-8aee9cf6e82a4b28a59a176ee47b63e5
Source dataset
uspto-grants-1992_06
Patent number
US05126366

Reaction notes

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