Methylamine → HCID 19874521, compound

HRID 465419Notes

Reaction equation

HRID 465419 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:35]=[CH:36][CH:37]=1)[CH:5]([OH:34])[CH2:6][NH:7][CH:8]([CH3:33])[CH2:9][C:10]1[CH:32]=[CH:31][C:13]([O:14][CH2:15][C:16]2O[CH:18]=[C:19]([O:23]CC3C=CC=CC=3)[C:20](=[O:22])[CH:21]=2)=[CH:12][CH:11]=1.[CH3:38][NH2:39]>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:35]=[CH:36][CH:37]=1)[CH:5]([OH:34])[CH2:6][NH:7][CH:8]([CH3:33])[CH2:9][C:10]1[CH:32]=[CH:31][C:13]([O:14][CH2:15][C:16]2[N:39]([CH3:38])[CH:18]=[C:19]([OH:23])[C:20](=[O:22])[CH:21]=2)=[CH:12][CH:11]=1

Participants

3

Reactant 2

HCID 6329MethylamineHCID 19874497HCID 19874497, compound

Product 1

HCID 19874521HCID 19874521, compound

Procedure

A suspension of 2-[4-[2 [(3-chloro-β-hydroxyphenethyl)amino]propyl]phenoxymethyl]-5-benzyloxy-4H-pyran-4-one (1.0 g) in 33% ethanolic methylamine solution (15 ml), was heated to 120° in a sealed vessel for 18 hours. The solvent was evaporated in vacuo and the residue purified by column chromatography on silica using chloroform, then 10% methanol:chloroform as eluent. The resulting gum was dissolved in methanol and 2M hydrochloric acid was added dropwise to bring the pH to 1.5-2.0. The solution was then hydrogenated at room temperature and pressure over 10% palladium on charcoal. After filtration and evaporation of solvent in vacuo the residue was treated with 1.2M sodium hydrogen carbonate solution (5 ml), and extracted with ethyl acetate (3×50 ml), and dried (MgSO4). After filtration and evaporation of solvent the residue was triturated with acetone to give 2-[4-[2-[(3-chloro-β-hydroxyphenethyl)amino]propyl]phenoxymethyl]-5-hydroxy-1-methyl-1H-pyrid-4-one (0.7 g) as a (40:60) mixture of diastereoisomers.

Workup

  1. temperaturewas heated to 120° in a sealed vessel for 18 hours
  2. customThe solvent was evaporated in vacuo
  3. customthe residue purified by column chromatography on silica
  4. dissolutionThe resulting gum was dissolved in methanol
  5. addition2M hydrochloric acid was added dropwise
  6. customwas then hydrogenated at room temperature
  7. filtrationAfter filtration and evaporation of solvent in vacuo the residue
  8. additionwas treated with 1.2M sodium hydrogen carbonate solution (5 ml)
  9. extractionextracted with ethyl acetate (3×50 ml)
  10. dry with materialdried (MgSO4)
  11. filtrationAfter filtration and evaporation of solvent the residue
  12. customwas triturated with acetone

Sources & evidence

ORD record
ord-292045c95a3a4d8ba25db2ed60f640d4
Source dataset
uspto-grants-1992_10
Patent number
US05153210

Reaction notes

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