Triethylamine → 4-[(R)-3-(2-Methyl-pyridin-4-yl)-3-oxo-1-o-tolyl-propyl]-benzoic acid methyl ester

HRID 1617794Notes

Reaction equation

HRID 1617794 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])[CH2:9][C:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[CH:13]=2)=[O:11])=[CH:4][CH:3]=1.C(N(CC)CC)C.[Cl-].[NH4+].[C:35]([O:38][CH2:39]C)(=[O:37])C>CO.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].ClCCl>[CH3:39][O:38][C:35](=[O:37])[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])[CH2:9][C:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[CH:13]=2)=[O:11])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 66666695(R)-3-(4-Bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one

Product 1

HCID 666668344-[(R)-3-(2-Methyl-pyridin-4-yl)-3-oxo-1-o-tolyl-propyl]-benzoic acid methyl esterYield 87%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of (R)-3-(4-bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one (example 142, step 2, 100 mg) in methanol (1.5 mL) and ethyl acetate (1.5 mL) were added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (10 mg), triethylamine (53.3 μL) at room temperature. The reaction mixture was stirred at 130° C. for 20 h under a carbon monoxide atmosphere (70 bar). A saturated aq. solution of ammonium chloride was added, the phases were separated and the inorganic one was extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (ethyl acetate/n-heptane 0:1 to 1:0) to yield the title compound as a colourless oil (95 mg, 87%), MS (ESI+): m/z=374.1 ([M+H]+).

Workup

  1. customthe phases were separated
  2. extractionthe inorganic one was extracted with ethyl acetate (2×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography on silica gel (ethyl acetate/n-heptane 0:1 to 1:0)

Sources & evidence

ORD record
ord-2b9c369195074558a0e511005a7692a3
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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