Methyl Acrylate → 3-{4-[3-(2-Methyl-pyridin-4-yl)-3-oxo-1-o-tolyl-propyl]-phenyl}-acrylic acid methyl ester

HRID 1617520Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([CH: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.[Cl-].[NH4+].[C:28]([O:32][CH3:33])(=[O:31])[CH:29]=[CH2:30]>CN(C=O)C.C(N(CC)CC)C.CCOC(C)=O>[CH3:33][O:32][C:28](=[O:31])[CH:29]=[CH:30][C:2]1[CH:7]=[CH:6][C:5]([CH: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

Conditions

Temperature: 100 °C

Procedure

To 3-(4-bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one ((example 74, step 5), 300 mg) in DMF (3 mL) tetrakis(triphenylphosphine)palladium (130 mg), methyl acrylate (0.103 mL) and triethylamine (0.16 mL) were added. The reaction mixture was stirred at 100° C. overnight, was cooled to room temperature and diluted with EtOAc and a saturated solution of ammonium chloride. The phases were separated and the inorganic one extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (EtOAc/n-heptane 1:1) to yield the title compound (62 mg, 20%) as a yellow oil, MS (ESI+): m/z=400.1912 ([M+H]+).

Workup

temperaturewas cooled to room temperature
customThe phases were separated
extractionthe inorganic one extracted with EtOAc
washThe combined organic layers were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified by flash chromatography on silica gel (EtOAc/n-heptane 1:1)

Sources & evidence

ORD record: ord-6a579b1d5c7a4e94aff8dd763ff4a69a
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765730B2

Reaction notes

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