Hydrochloric Acid → 6-Oxo-(3-quinolin-3-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid

HRID 1837924Notes

Reaction equation

HRID 1837924 reaction equation
COP([CH2:7][C:8](=[O:22])[CH2:9][CH2:10][CH2:11][C:12]1[CH:21]=[CH:20][C:19]2[CH2:18][CH2:17][CH2:16][NH:15][C:14]=2[N:13]=1)(=O)OC.[Li+].[Cl-].C([O:27][C:28](=[O:43])[CH2:29][CH:30]([C:33]1[CH:34]=[N:35][C:36]2[C:41]([CH:42]=1)=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:31]=O)C.C1CCN2C(=NCCC2)CC1.[Li+].[OH-].Cl>C(#N)C.CCO.[Pd].O>[O:22]=[C:8]([CH2:9][CH2:10][CH2:11][C:12]1[CH:21]=[CH:20][C:19]2[CH2:18][CH2:17][CH2:16][NH:15][C:14]=2[N:13]=1)[CH2:7][CH2:31][CH:30]([C:33]1[CH:34]=[N:35][C:36]2[C:41]([CH:42]=1)=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH2:29][C:28]([OH:43])=[O:27]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 433294Lithium ChlorideHCID 537991904-Oxo-3-(quinolin-3-yl)-butyric acid ethyl esterHCID 538016292-Oxo-5-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)-pentyl-phosphonic acid dimethyl ester

Product 1

HCID 101598546-Oxo-(3-quinolin-3-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

Ketophosphonate 22-5 (1.0 g, 3.1 mmol), anhydrous LiCl (170 mg, 4.0 mmol), and 22-4 (0.797 g, 3.1 mmol) in anhydrous acetonitrile (60 mL), was treated with DBU (0.52 mL, 3.3 mmol) and the resulting suspension stirred at room temperature for 1 h. The solvent was removed at reduced pressure and the resulting residue partitioned between brine and methylene chloride. The organic layer was removed, dried, and concentrated to afford 22-6 as mixture of E and Z olefins. The crude mixture was dissolved in EtOH (50 mL), treated with 10% Pd/C (200 mg) and stirred under a hydrogen filled balloon for 4 h, then filtered. The filtrate was treated with LiOH (2.0 eq) and water (20 mL) and stirred at room temperature for 12 h, then neutralized with 1N HCl and evaporated Chromatography on silica gel (10% MeOH/methylene chloride) afforded 22-7 as a white solid.

Workup

  1. customThe solvent was removed at reduced pressure
  2. customthe resulting residue partitioned between brine and methylene chloride
  3. customThe organic layer was removed
  4. customdried
  5. concentrationconcentrated
  6. customto afford 22-6
  7. stirringstirred under a hydrogen filled balloon for 4 h
  8. filtrationfiltered
  9. stirringstirred at room temperature for 12 h
  10. customevaporated Chromatography on silica gel (10% MeOH/methylene chloride)

Sources & evidence

ORD record
ord-c91802f243b14779a591365d0d109df5
Source dataset
uspto-grants-2004_08
Patent number
US06784190B2

Reaction notes

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