Sodium Carbonate → 5-(3,5-Dimethoxy-phenyl)-quinoline-8-carboxylic acid

HRID 43192Notes

Reaction equation

HRID 43192 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.Br[C:15]1[CH:24]=[CH:23][C:22]([C:25]([OH:27])=[O:26])=[C:21]2[C:16]=1[CH:17]=[CH:18][CH:19]=[N:20]2.C([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+]>CCO.C1(C)C=CC=CC=1.CCOC(C)=O.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:15]2[CH:24]=[CH:23][C:22]([C:25]([OH:27])=[O:26])=[C:21]3[C:16]=2[CH:17]=[CH:18][CH:19]=[N:20]3)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1

Participants

10

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 4374257(3,5-Dimethoxyphenyl)boronic acidHCID 592928605-Bromoquinoline-8-carboxylic acid

Product 1

HCID 592928765-(3,5-Dimethoxy-phenyl)-quinoline-8-carboxylic acidYield 81%

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 3,5-dimethoxyphenylboronic acid (217 mg, 1.19 mmol, 1.2 equiv) (Step 1.8) in EtOH (0.5 mL) was added dropwise to a mixture of 5-bromo-quinoline-8-carboxylic acid (Step 159.3) (250 mg, 0.99 mmol), PdCl2(dppf) (22 mg, 0.03 mmol, 0.03 equiv), Na2CO3 (2M solution in H2O, 1 mL, 3.97 mmol, 4 equiv) in toluene (5 mL) at 105° C., under an argon atmosphere. The reaction mixture was stirred at 105° C. for 1 h, allowed to cool to rt, diluted with EtOAc and H2O, basified by addition of a 2N aqueous solution of NaOH (2 mL), filtered through a pad of celite and the filtrate was extracted with EtOAc. The aqueous layer was separated and acidified to pH 5. The resulting precipitate was collected by vacuum filtration to provide 248 mg of the title compound as a white solid: ESI-MS: 310.1 [M+H]+; tR=4.06 min (System 1).

Workup

  1. temperatureto cool to rt
  2. filtrationfiltered through a pad of celite
  3. extractionthe filtrate was extracted with EtOAc
  4. customThe aqueous layer was separated
  5. filtrationThe resulting precipitate was collected by vacuum filtration

Sources & evidence

ORD record
ord-3bf40791a5b34a20b2709d8368665a72
Source dataset
uspto-grants-2013_09
Patent number
US08536175B2

Reaction notes

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