Hydrochloric Acid → 1-(4-Fluorophenyl)-6-hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

HRID 1048878Notes

Reaction equation

HRID 1048878 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[CH:7]=[C:6]([C:19]([O:21]CC)=[O:20])[C:5]2=[O:24].[OH-:25].[K+].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.Cl>O1CCOCC1.O.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:18][C:15]1[CH:16]=[CH:17][C:12]([N:8]2[C:9]3[C:4](=[CH:3][C:2]([OH:25])=[CH:11][CH:10]=3)[C:5](=[O:24])[C:6]([C:19]([OH:21])=[O:20])=[CH:7]2)=[CH:13][CH:14]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 121447944Ethyl 6-bromo-1-(4-fluorophenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate

Product 1

HCID 1214479811-(4-Fluorophenyl)-6-hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acidYield 100%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

Compound D (500 mg, 1.28 mmol, 1.00 eq), potassium hydroxide (216 mg, 3.84 mmol, 3.00 eq), tris(dibenzylideneacetone)dipalladium(0) (70.4 mg, 0.0769 mmol, 0.0600 eq) and 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (65.3 mg, 0.154 mmol, 0.120 eq) were suspended in a mixture of 1,4-dioxane (3.2 mL) and water (3.2 mL) in a microwave vial and heated in a microwave reactor at 150° C. for 15 minutes. The reaction was neutralized with 2N HCl and the mixture was diluted with ethyl acetate and washed with water. The organic phase was dried (MgSO4), filtered and concentrated in vacuo to afford 383 mg (99%) of the title compound as a brown solid that was used without further purification. 1H NMR (400 MHz, DMSO-d6) δ 8.56 (s, 1H), 7.75-7.72 (m, 2H), 7.67 (d, J=2.7 Hz, 1H), 7.51 (t, J=8.7 Hz, 2H), 7.26 (d, J=9.1 Hz, 1H), 6.99 (d, J=9.2 Hz, 1H); ES-MS [M+1]+: 300.2.

Workup

  1. washwashed with water
  2. dry with materialThe organic phase was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dfb3fe4dc6e541dc8b4c612a2b0e358e
Source dataset
uspto-grants-2016_07
Patent number
US09382208B1

Reaction notes

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