Water → 4'-[3-(1-Methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-3-oxo-1-o-tolyl-propyl]-biphenyl-4-carboxylic acid

HRID 1617638Notes

Reaction equation

HRID 1617638 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[CH3:26])[CH2:9][C:10]([C:12]2[CH:13]=[CH:14][C:15](=[O:19])[N:16]([CH3:18])[CH:17]=2)=[O:11])=[CH:4][CH:3]=1.[C:27]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)([OH:29])=[O:28].O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.[CH-]1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=C1.[CH-]1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=C1.Cl[Pd]Cl.[Fe+2]>[CH3:18][N:16]1[C:15](=[O:19])[CH:14]=[CH:13][C:12]([C:10](=[O:11])[CH2:9][CH:8]([C:5]2[CH:4]=[CH:3][C:2]([C:33]3[CH:34]=[CH:35][C:30]([C:27]([OH:29])=[O:28])=[CH:31][CH:32]=3)=[CH:7][CH:6]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[CH3:26])=[CH:17]1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 3121834-Carboxyphenylboronic AcidHCID 666685075-[3-(4-Bromo-phenyl)-3-o-tolyl-propionyl]-1-methyl-1H-pyridin-2-one

Product 1

HCID 670155774'-[3-(1-Methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-3-oxo-1-o-tolyl-propyl]-biphenyl-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred suspension of 5-[3-(4-bromo-phenyl)-3-o-tolyl-propionyl]-1-methyl-1H-pyridin-2-one (50 mg, example 162, step 3) and 4-carboxyphenylboronic acid (32 mg) in 1,4-dioxane (0.4 ml) under argon were added dichloro(1,1′-bis(diphenylphosphino)ferrocene)-palladium(II) dichloromethane adduct (4.5 mg), water (0.3 ml) and 2 M aqueous sodium carbonate solution (0.18 ml). The mixture was stirred at 80° C. for 2 h. After cooling to room temperature, the mixture was filtered. The filter cake was washed with ethyl acetate and with a saturated KHSO4 solution. The combined filtrate was extracted with ethyl acetate. The organic phase was dried (MgSO4), filtered and concentrated to dryness. The product was purified by chromatography (SiO2, dichloromethane/methanol 1:0 to 9:1) to give the title compound (75 mg, not totally pure) as a colorless solid, MS (ESI−): m/z=450.2 [M−H]−.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture was filtered
  3. washThe filter cake was washed with ethyl acetate and with a saturated KHSO4 solution
  4. extractionThe combined filtrate was extracted with ethyl acetate
  5. dry with materialThe organic phase was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe product was purified by chromatography (SiO2, dichloromethane/methanol 1:0 to 9:1)

Sources & evidence

ORD record
ord-7865b68c2cb449239aabec2ddf98e271
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

Loading…