Sodium Hydroxide → 2,8-Dimethylquinoline-7-carboxylic acid

HRID 339022Notes

Reaction equation

HRID 339022 reaction equation
Br[C:2]1[C:11]([CH3:12])=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([CH3:13])=[N:9]2)=[CH:4][CH:3]=1.C([O:16][C:17](=[O:21])C([O-])=O)C.[K+].[OH-].[Na+]>CN1C(=O)CCC1.O.C(O)(C(F)(F)F)=O.C(O)(C(F)(F)F)=O.[Pd]>[CH3:13][C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[C:11]([CH3:12])[C:2]([C:17]([OH:21])=[O:16])=[CH:3][CH:4]=2)[N:9]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 23678856Ethanedioic acid, 1-ethyl ester, potassium salt (1:1)HCID 455994557-Bromo-2,8-dimethylquinoline

Product 1

HCID 709835712,8-Dimethylquinoline-7-carboxylic acidYield 54%

Reagents, catalysts & solvents 3

HCID 4378622PD(Tfa)2CatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

A 250 mL round-bottomed flask was charged with 7-bromo-2,8-dimethylquinoline (2.0 g, 8.47 mmol), potassium 2-ethoxy-2-oxoacetate (1.98 g, 12.7 mmol) and dcpp-2HBF4 (0.311 g, 0.508 mmol) in anhydrous NMP (28 mL) and nitrogen was bubbled into the mixture for 10 minutes, followed by the addition of Pd(TFA)2 (0.085 g, 0.254 mmol). The mixture was heated at 150° C. in an oil bath under a nitrogen atmosphere for 18 hours. The reaction mixture was cooled to ambient temperature and treated with a 2N NaOH solution (20 mL), and the mixture stirred at ambient temperature for 18 hours. The mixture was diluted with water (100 mL) and washed with ethyl acetate (180 mL). The aqueous layer was adjusted to pH 3 with 6N HCl and extracted with a 10% IPA-ethyl acetate solution. The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by reverse phase chromatography (Biotage SP4, 40M, C-18; 0-40% MeCN—H2O) to afford 2,8-dimethylquinoline-7-carboxylic acid (0.921 g, 54% yield).

Workup

  1. customwas bubbled into the mixture for 10 minutes
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. washwashed with ethyl acetate (180 mL)
  4. extractionextracted with a 10% IPA-ethyl acetate solution
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by reverse phase chromatography (Biotage SP4, 40M, C-18; 0-40% MeCN—H2O)

Sources & evidence

ORD record
ord-36ff14a869ce4014beceaa5e5f89ebc3
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

Loading…