Potassium Carbonate → tert-Butyl 4-({2-[4-(2-bromo-5-chlorophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]propanoyl}amino)benzoate

HRID 56838Notes

Reaction equation

HRID 56838 reaction equation
Br[C:2]1[C:7]([O:8][CH3:9])=[CH:6][N:5]([CH:10]([CH3:27])[C:11]([NH:13][C:14]2[CH:26]=[CH:25][C:17]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:16][CH:15]=2)=[O:12])[C:4](=[O:28])[CH:3]=1.[Br:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1>[Br:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=1[C:2]1[C:7]([O:8][CH3:9])=[CH:6][N:5]([CH:10]([CH3:27])[C:11]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])=[CH:25][CH:26]=2)=[O:12])[C:4](=[O:28])[CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 445581362-Bromo-5-chlorophenylboronic acid2×HCID 117622877tert-Butyl 4-{[2-(4-bromo-5-methoxy-2-oxopyridin-1(2H)-yl)propanoyl]amino}benzoate

Product 1

HCID 117622595tert-Butyl 4-({2-[4-(2-bromo-5-chlorophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]propanoyl}amino)benzoate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Under argon (in a flask dried by heating), 113 mg (0.25 mmol) of tert-butyl 4-{[2-(4-bromo-5-methoxy-2-oxopyridin-1(2H)-yl)propanoyl]amino}benzoate (racemate), 70 mg (0.30 mmol, 1.2 eq.) of 2-bromo-5-chlorophenylboronic acid, 103 mg (0.74 mmol, 3.0 eq.) of potassium carbonate and 20 mg (0.03 mmol, 0.1 eq.) of [1,1-bis(diphenylphosphino)ferrocene]palladium(II) chloride/dichloromethane monoadduct were suspended in 5.0 ml of dioxane and stirred overnight in an oil bath already preheated to 110° C. A further 10 mg (0.01 mmol, 0.05 eq.) of [1,1-bis-(diphenylphosphino)ferrocene]palladium(II) chloride/dichloromethane monoadduct and 29 mg (0.12 mmol, 0.5 eq.) of 2-bromo-5-chlorophenylboronic acid were added and the reaction mixture was stirred at 110° C. for a further night and then filtered through Celite. The residue was washed with dioxane. The combined filtrates were concentrated under reduced pressure. The residue was triturated with water, filtered off, dried under reduced pressure and purified by flash chromatography (silica gel 50, cyclohexane/ethyl acetate gradient). Yield: 72 mg (purity 73%, 38% of theory)

Workup

  1. customalready preheated to 110° C
  2. stirringthe reaction mixture was stirred at 110° C. for a further night
  3. filtrationfiltered through Celite
  4. washThe residue was washed with dioxane
  5. concentrationThe combined filtrates were concentrated under reduced pressure
  6. customThe residue was triturated with water
  7. filtrationfiltered off
  8. customdried under reduced pressure
  9. custompurified by flash chromatography (silica gel 50, cyclohexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-73dc47a899eb4a4587ae2cf54f63a7e9
Source dataset
uspto-grants-2016_09
Patent number
US09434690B2

Reaction notes

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