Hydrochloric Acid → 5-Fluoro-3-hydroxy-6-methoxy-quinoline-4-carbaldehyde

HRID 633829Notes

Reaction equation

HRID 633829 reaction equation
Cl[C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH:12]=[O:13])=[C:9]([F:14])[C:8]([O:15][CH3:16])=[CH:7][CH:6]=2.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[OH-:51].[K+].Cl>O1CCOCC1.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].C(OCC)(=O)C.O>[F:14][C:9]1[C:8]([O:15][CH3:16])=[CH:7][CH:6]=[C:5]2[C:10]=1[C:11]([CH:12]=[O:13])=[C:2]([OH:51])[CH:3]=[N:4]2

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 867307093-Chloro-5-fluoro-6-methoxy-quinoline-4-carbaldehyde

Product 1

HCID 866715305-Fluoro-3-hydroxy-6-methoxy-quinoline-4-carbaldehydeYield 36%

Reagents, catalysts & solvents 4

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

Procedure

Tris(dibenzylideneacetone)dipalladium(0) (40 mg, 0.04 mmol, 0.02 eq) is added at room temperature to a stirred solution of 3-chloro-5-fluoro-6-methoxy-quinoline-4-carbaldehyde (500 mg, 2.10 mmol, 1.0 eq) in dioxane (6 mL), followed by 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (100 mg, 0.21 mmol, 0.1 eq) and a 1.6 M potassium hydroxide aqueous solution (2 mL). The reaction mixture is irradiated by microwaves at 125° C. for 15 minutes, then water (10 mL) is added, the resulting mixture is neutralized with 2.0 N hydrochloric acid aqueous solution and extracted with ethyl acetate (3×10 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a crude product that is purified by column chromatography (silica gel, eluent: petroleum ether:ethyl acetate, 5:1, v/v) to afford 5-fluoro-3-hydroxy-6-methoxy-quinoline-4-carbaldehyde as a light yellow solid (168 mg, 36% yield).

Workup

  1. customThe reaction mixture is irradiated by microwaves at 125° C. for 15 minutes
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. dry with materialThe combined organic layers are dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a crude product that
  7. customis purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-9ffcc739d8fa45658f1b1e043264b15d
Source dataset
uspto-grants-2016_04
Patent number
US09321788B2

Reaction notes

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