Potassium Carbonate → 6-Methyl-4-oxo-5-(3-trifluoromethyl-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid

HRID 512490Notes

Reaction equation

HRID 512490 reaction equation
Br[C:2]1[C:3](=[O:12])[C:4]([C:9]([OH:11])=[O:10])=[CH:5][NH:6][C:7]=1[CH3:8].[F:13][C:14]([F:25])([F:24])[C:15]1[CH:16]=[C:17](B(O)O)[CH:18]=[CH:19][CH:20]=1.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[CH3:8][C:7]1[NH:6][CH:5]=[C:4]([C:9]([OH:11])=[O:10])[C:3](=[O:12])[C:2]=1[C:19]1[CH:18]=[CH:17][CH:16]=[C:15]([C:14]([F:25])([F:24])[F:13])[CH:20]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 183299675-Bromo-4-hydroxy-6-methylpyridine-3-carboxylic acid

Product 1

HCID 867115326-Methyl-4-oxo-5-(3-trifluoromethyl-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 5-bromo-6-methyl-4-oxo-1,4-dihydro-pyridine-3-carboxylic acid (preparation 5a, 12.05 g, 51.9 mmol), 3-(trifluoromethyl)phenylboronic acid (13.6 g, 71.6 mmol), 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (3.60 g, 4.92 mmol) in acetonitrile (100 mL) is added 2 M aqueous K2CO3 solution (47 mL, 94 mmol). After stirring for 6 h at 75° C., the reaction mixture is filtered and the filtrate is concentrated under reduced pressure. The resulting residue is dissolved in dichloromethane and extracted several times with water. The combined aqueous layer is acidified with 4 N aqueous HCl. The formed precipitate is filtered off, washed with 50 mL hexanes/ethyl acetate (4:1) and dried. Yield: 13.5 g (88% of theory); ESI mass spectrum: [M+H]+=298; Retention time HPLC: 0.80 min (Z003—001).

Workup

  1. filtrationthe reaction mixture is filtered
  2. concentrationthe filtrate is concentrated under reduced pressure
  3. dissolutionThe resulting residue is dissolved in dichloromethane
  4. extractionextracted several times with water
  5. filtrationThe formed precipitate is filtered off
  6. washwashed with 50 mL hexanes/ethyl acetate (4:1)
  7. customdried
  8. custom0.80 min (Z003—001)

Sources & evidence

ORD record
ord-cc7233cc02f6462a9ee5a2aa68f3f530
Source dataset
uspto-grants-2015_08
Patent number
US09102624B2

Reaction notes

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