Diethyl Ether → 3-[3-(5-Isopropyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-5-methyl-phenyl]-acrylonitrile

HRID 2194748Notes

Reaction equation

HRID 2194748 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]([C:11]2[C:16]([CH:17]([CH3:19])[CH3:18])=[C:15]([O:20][CH3:21])[N:14]=[C:13]([O:22][CH3:23])[N:12]=2)=[O:10])[CH:5]=[C:6]([CH3:8])[CH:7]=1.C([O-])(=O)C.[Na+].[C:29](#[N:32])[CH:30]=[CH2:31].CCOCC>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[CH:17]([C:16]1[C:11]([C:9]([C:4]2[CH:3]=[C:2]([CH:31]=[CH:30][C:29]#[N:32])[CH:7]=[C:6]([CH3:8])[CH:5]=2)=[O:10])=[N:12][C:13]([O:22][CH3:23])=[N:14][C:15]=1[O:20][CH3:21])([CH3:19])[CH3:18]

Participants

9

Reactant 4

HCID 3283Diethyl EtherHCID 7855AcrylonitrileHCID 517045Sodium AcetateHCID 59686860(3-Bromo-5-methyl-phenyl)-(5-isopropyl-2,6-dimethoxy-pyrimidin-4-yl)-methanone

Product 1

HCID 667055443-[3-(5-Isopropyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-5-methyl-phenyl]-acrylonitrileYield 17%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
111 °C

Procedure

To a stirred solution of (3-bromo-5-methyl-phenyl)-(5-isopropyl-2,6-dimethoxy-pyrimidin-4-yl)-methanone (3.79 g, 10 mmol) in anhydrous DMF (10 mL), was added sodium acetate (902 mg, 11 mmol), palladium acetate (224 mg, 1 mmol), tetrakis(triphenylphosphine)palladium(0) (1.049 g, 4 mmol), and acrylonitrile in this order. The mixture was then stirred at 90-132° C. (oil bath) for about 23 hr. After cooling to room temperature, ether and ethyl acetate (2:1) was added to the reaction mixture. The mixture was then washed with aqueous saturated sodium bicarbonate solution, washed with water twice, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexanes (1:4)) to afford 595 mg (17%) of a white solid. Z-isomer (275 mg, 8%) was also obtained as a white solid. m.p. 144-145° C.; 1H NMR (300 MHz, CDCl3) δ 1.19 (6H, d, J=6.9 Hz), 2.42 (3H, s), 2.83 (1H, m), 3.94 (3H, s), 4.08 (3H, s), 5.92 (1H, d, J=16.8 Hz), 7.39 (1H, d, J=16.8 Hz), 7.49 (1H, s), 7.69 (1H, s), 7.75 (1H, s).

Workup

  1. temperatureAfter cooling to room temperature
  2. washThe mixture was then washed with aqueous saturated sodium bicarbonate solution
  3. washwashed with water twice
  4. dry with materialdried with anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexanes (1:4))

Sources & evidence

ORD record
ord-b610a80aa83440079d1ebbfbf8a09ae1
Source dataset
uspto-grants-2012_12
Patent number
US08334295B2

Reaction notes

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