Sodium Iodide → HCID 53909603, compound

HRID 374214Notes

Reaction equation

HRID 374214 reaction equation
[OH:1][C:2]1[CH:13]=[CH:12][C:5]2[O:6][C@@H:7]([CH2:10][NH2:11])[CH2:8][O:9][C:4]=2[CH:3]=1.Cl[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.[I-].[Na+]>CN(C=O)C>[OH:1][C:2]1[CH:13]=[CH:12][C:5]2[O:6][C@@H:7]([CH2:10][NH:11][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)[CH2:8][O:9][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 19006662H-1-Benzopyran-2-one, 7-(3-chloropropoxy)-HCID 54083614HCID 54083614, compound

Product 1

HCID 53909603HCID 53909603, compoundYield 12.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-2,3-Dihydro-6-hydroxy-1,4-benzodioxin-2-methanamine (2.89 g, 16.0 mmole), 7-(3-chloropropoxy)coumarin (3.46 g, 14.5 mmole), diisopropylethylamine (12.5 ml, 72 mmole) and sodium iodide (2.20 g, 14.7 mmole) were combined in 200 ml of DMF and heated at 80°-100° C. for 24 hours under a nitrogen atmosphere. The solvent was then removed in vacuum. The residue was column chromatographed on silica gel using first 0.5% methanol/dichloromethane, then 1% methanol/dichloromethane, and finally 3% methanol/dichloromethane as eluant. The product-containing fractions (Rf=0.45 on silica gel with 5% methanol/dichloromethane) were combined and rechromatographed on 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 pure free base (0.98 g) redissolved in methanol and boiled on a hot plate, the methanol gradually being replaced with isopropanol. 4N HCl/isopropanol (7.0 ml) was added and the title compound was collected by filtration and dried in vacuum at 80° C. The procedure yielded 0.71 g of white solid, monohydrochloride, m.p. 236°-239° C.

Workup

  1. temperatureheated at 80°-100° C. for 24 hours under a nitrogen atmosphere
  2. customThe solvent was then removed in vacuum
  3. customchromatographed on silica gel using first 0.5% methanol/dichloromethane
  4. customrechromatographed on silica gel using first 75% ethyl acetate/dichloromethane
  5. concentrationThe product-containing fractions were concentrated in vacuum
  6. dissolutionthe pure free base (0.98 g) redissolved in methanol
  7. addition4N HCl/isopropanol (7.0 ml) was added
  8. filtrationthe title compound was collected by filtration
  9. customdried in vacuum at 80° C

Sources & evidence

ORD record
ord-409028d812c145728725a037b836232c
Source dataset
uspto-grants-1992_11
Patent number
US05166367

Reaction notes

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