Methyl Acrylate → 6-methoxy-2H-1-oxa-5,9-diaza-phenanthrene-3-carboxylic acid methyl ester

HRID 633795Notes

Reaction equation

HRID 633795 reaction equation
N12CCN(CC1)CC2.[OH:9][C:10]1[CH:11]=[N:12][C:13]2[C:18]([C:19]=1[CH:20]=O)=[N:17][C:16]([O:22][CH3:23])=[CH:15][CH:14]=2.C(N(CC)CC)C.CS(Cl)(=O)=O.[CH3:36][O:37][C:38](=[O:41])[CH:39]=[CH2:40]>C(OCC)(=O)C>[CH3:36][O:37][C:38]([C:39]1[CH2:40][O:9][C:10]2[CH:11]=[N:12][C:13]3[C:18]([C:19]=2[CH:20]=1)=[N:17][C:16]([O:22][CH3:23])=[CH:15][CH:14]=3)=[O:41]

Participants

7

Reactant 5

HCID 7294Methyl AcrylateHCID 8471TriethylamineHCID 9237DabcoHCID 31297Methanesulfonyl chlorideHCID 1363413973-Hydroxy-6-methoxy-[1,5]naphthyridine-4-carbaldehyde

Product 1

HCID 711187386-methoxy-2H-1-oxa-5,9-diaza-phenanthrene-3-carboxylic acid methyl esterYield 53%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

1,4-Diazabicyclo[2.2.2]octane (522 mg, 4.65 mmol, 1.0 eq) is added at room temperature to a stirred suspension of 3-hydroxy-6-methoxy-[1,5]naphthyridine-4-carbaldehyde (950 mg, 4.65 mmol, 1.0 eq) in acrylic acid methyl ester (20 mL) and the resulting mixture is heated under reflux for 3 hours. The reaction mixture is then cooled down to room temperature, solvent is removed and the residue is dissolved in 1,2-dichloroethane (20 mL). Triethylamine (19.5 mL, 139.6 mmol, 30.0 eq) is then added at 0° C., followed by methanesulfonyl chloride (3.85 mL, 69.8 mml, 15.0 eq) and the resulting mixture is heated under reflux for 4 hours. Solvent is removed and the residue is extracted with dichloromethane (3×40 mL) and water (40 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel, eluent: petroleum ether:ethyl acetate, 10:1 to 5:1, v/v) to afford 6-methoxy-2H-1-oxa-5,9-diaza-phenanthrene-3-carboxylic acid methyl ester as a light yellow oil (670 mg, 53% yield).

Workup

  1. temperaturethe resulting mixture is heated
  2. temperatureunder reflux for 3 hours
  3. customsolvent is removed
  4. dissolutionthe residue is dissolved in 1,2-dichloroethane (20 mL)
  5. temperaturethe resulting mixture is heated
  6. temperatureunder reflux for 4 hours
  7. customSolvent is removed
  8. extractionthe residue is extracted with dichloromethane (3×40 mL) and water (40 mL)
  9. dry with materialThe combined organic layers are dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto give a residue that
  13. customis purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-9873e5491ff5432fa69e55bfc8253e9c
Source dataset
uspto-grants-2016_04
Patent number
US09321788B2

Reaction notes

Loading…