Potassium Phosphate, Tribasic → HCID 24822773, compound

HRID 1925301Notes

Reaction equation

HRID 1925301 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[F:16].[OH:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[C:24]([C:28]([OH:30])=[O:29])=[CH:23][CH:22]=[CH:21]2.C(P(C(C)(C)C)C1C=CC=CC=1C1C(CCC)=CC(CCC)=CC=1CCC)(C)(C)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[F:16][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[O:17][C:18]1[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=1)[C:24]([C:28]([OH:30])=[O:29])=[CH:23][CH:22]=[CH:21]3)=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][CH3:15])[CH:7]=2

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 54638006-Hydroxy-1-naphthoic acidHCID 11481892HCID 11481892, compoundHCID 67346612HCID 67346612, compound

Product 1

HCID 24822773HCID 24822773, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A resealable tube was charged with 4-chloro-3-fluoro-6,7-dimethoxyquinoline (prepared by the method described in WO 98/13350) (0.610 g, 2.52 mmol), 6-hydroxy-1-naphthoic acid (0.474 g, 2.52 mmol), palladium acetate (0.023 g, 0.101 mmol), 2-di-t-butylphosphino-2′,4′,6′-tri-1-propyl-1,1′-biphenyl (0.086 g, 0.202 mmol), potassium phosphate (2.14 g, 10.08 mmol), and DMF (12.6 mL, Aldrich). The system was flushed with argon and the tube was sealed. The mixture was stirred at 100° C. for 19 h then cooled to RT. Water (13 mL) was added, and the pH was adjusted to 6-7 with aqueous 6 N HCl solution. The resulting precipitate was filtered, washed with water, and purified by column chromatography on silica gel (eluting with 0-100% (50:50:2, EtOAc:hexane:AcOH)) to afford 6-(3-fluoro-6,7-dimethoxyquinolin-4-yloxy)-1-naphthoic acid as an off-white solid. MS (ESI, pos. ion) m/z: 394.0 (M+H). Mass Calc'd for C22H16FNO5: 393.1

Workup

  1. customprepared by the method
  2. customThe system was flushed with argon
  3. customthe tube was sealed
  4. temperaturethen cooled to RT
  5. additionWater (13 mL) was added
  6. filtrationThe resulting precipitate was filtered
  7. washwashed with water
  8. custompurified by column chromatography on silica gel (eluting with 0-100% (50:50:2, EtOAc:hexane:AcOH))

Sources & evidence

ORD record
ord-76a66a69a6e441e395e1e3ee8826a1a1
Source dataset
uspto-grants-2012_05
Patent number
US08178557B2

Reaction notes

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