Methanol → HCID 22346370, compound

HRID 897332Notes

Reaction equation

HRID 897332 reaction equation
[OH:1][C:2]1[C:3]([C:20]([O:22][CH3:23])=[O:21])=[N:4][C:5](OS(C(F)(F)F)(=O)=O)=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[CH3:24][OH:25].C(N([CH:32]([CH3:34])[CH3:33])CC)(C)C>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:24]([O:1][C:2]1[C:11]2[N:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:5]([C:20]([O:22][CH3:23])=[O:21])=[N:4][C:3]=1[C:20]([O:22][CH3:23])=[O:21])(=[O:25])[C:33]1[CH:32]=[CH:34][CH:3]=[CH:2][CH:11]=1

Participants

7

Reactant 3

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 22346411HCID 22346411, compound

Product 1

HCID 22346370HCID 22346370, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of the compound of Step 3 (11.9 g, 26 mmol) in DMF (50 ml) was added methanol (11 ml, 290 mmol), diisopropylethylamine (6.7 g, 9.3 ml, 52 mmol), Pd(OAc)2 (0.58 g, 2.6 mmol), and 1,1′-bis(diphenylphosphino)ferrocene (1.44 g, 2.6 mmol) while bubbling argon through the mixture. This was then placed in a bomb reactor and purged three times with carbon monoxide and finally filled to 80 p.s.i. and heated to 70° C. for two hours. The reaction mixture was then poured into water (˜150 ml). Ethyl acetate (50 ml) was then added to the mixture and the aqueous phase was extracted six times. The combined organics were dried over sodium sulfate, filtered and concentrated. The crude material was allowed to dry on the hi-vac overnight and was then suspended in ethyl acetate. The undesired solids (methyl 8-(benzoyloxy)-5-oxo-5,6-dihydro-1,6-naphthyridine-7-carboxylate) that did not dissolve were collected by vacuum filtration and set aside. This was repeated twice. To the EtOAc solution was then added hexanes and a few drops of diethyl ether and the mixture was placed in a sonicator for 15 minutes which allowed solids to crystallize out of the solution. The solids were collected by vacuum filtration.

Workup

  1. customwhile bubbling argon through the mixture
  2. customThis was then placed in a bomb reactor
  3. custompurged three times with carbon monoxide
  4. additionfinally filled to 80 p.s.i
  5. additionThe reaction mixture was then poured into water (˜150 ml)
  6. additionEthyl acetate (50 ml) was then added to the mixture
  7. extractionthe aqueous phase was extracted six times
  8. dry with materialThe combined organics were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto dry on the hi-vac overnight
  12. dissolutionThe undesired solids (methyl 8-(benzoyloxy)-5-oxo-5,6-dihydro-1,6-naphthyridine-7-carboxylate) that did not dissolve
  13. filtrationwere collected by vacuum filtration
  14. customto crystallize out of the solution
  15. filtrationThe solids were collected by vacuum filtration

Sources & evidence

ORD record
ord-944983c7136f429b9c8328c8916b7564
Source dataset
uspto-grants-2005_07
Patent number
US06921759B2

Reaction notes

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