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

HRID 426182Notes

Reaction equation

HRID 426182 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.CC(=O)OCC>[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, 1 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 ca. 23 hr. After cooling to room temperature, ether and EA (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, EA: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). Z isomer: 1H NMR (300 MHz, CDCl3) δ 1.19 (6H, d, J=7.2 Hz), 2.45 (3H, s), 2.84 (1H, m), 3.93 (3H, s), 4.06 (3H, s), 5.49 (1H, d, J=12.0 Hz), 7.11 (1H, d, J=12.0 Hz), 7.75 (1H, s), 7.90 (1H, s), 7.97 (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, EA:hexanes (1:4))

Sources & evidence

ORD record
ord-6518990ae20145da851be62dfed149d5
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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