Dimethylformamide → HCID 69204373, compound

HRID 2378327Notes

Reaction equation

HRID 2378327 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6](/[CH:12]=[CH:13]/[C:14]#[N:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].I[C:17]1[CH:18]=[CH:19][C:20]([O:24][CH3:25])=[C:21]([NH2:23])[CH:22]=1.C[C:27]([O-:29])=[O:28].[K+].[CH3:31]N(C=O)C>[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-].CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:31][O:29][C:27](=[O:28])[NH:23][C:21]1[CH:22]=[CH:17][C:18]([C:12]([C:6]2[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=2)=[CH:13][C:14]#[N:15])=[CH:19][C:20]=1[O:24][CH3:25].[NH2:23][C:21]1[CH:22]=[CH:17][C:18]([C:12]([C:6]2[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=2)=[CH:13][C:14]#[N:15])=[CH:19][C:20]=1[O:24][CH3:25]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 517044Potassium AcetateHCID 129053825-Iodo-2-methoxyanilineHCID 53623237HCID 53623237, compound

Product 2

HCID 69204373HCID 69204373, compoundHCID 77620386HCID 77620386, compound

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
165 °C

Procedure

In a 20-mL capacity microwave vessel was combined (E)-3-(3-ethoxy-4-methoxyphenyl)-acrylonitrile (0.41 g, 2.0 mmol), 5-iodo-2-methoxy-phenylamine (0.75 g, 1.5 equiv, 3.0 mmol), Pd(OAc)2 (45 mg, 10 mol %, 0.2 mmol), nBu4NBr (0.71 g, 1.1 equiv, 2.2 mmol), and KOAc (0.49 g, 2.5 equiv, 5.0 mmol) in DMF (8 mL). The mixture was purged with nitrogen gas for 30 seconds and the vessel was sealed. The reaction mixture was stirred in a microwave at 165° C. for 50 min, after which the starting material was consumed (TLC). The mixture was diluted with EtOAc (100 mL), washed with water (2×75 mL), and then brine (50 mL). The organic layer was dried (Na2SO4), filtered, and concentrated. The crude material was purified by column chromatography (SiO2, 7:3 hexanes/EtOAc). Concentration of the desired fractions afforded the title compound (Z)-(3-(4-amino-3-methoxy-phenyl)-3-(3-ethoxy-4-methoxy-phenyl)-acrylonitrile in 90% yield, as the major isomer of a 92:8 mixture: 1H NMR δ (400 M Hz, CDCl3) 7.02 (dd, 1H, J=8.4, 2.4 Hz), 6.98 (d, 1H, J=2.4 Hz), 6.90 (d, 1H, J=8.4 Hz), 6.75 (d, 1H, J=8.4 Hz), 6.70 (dd, 1H, J=8.4, 2.4 Hz), 6.65 (d, 1H, J=2.0 Hz), 5.51 (s, 1H), 4.08 (q, 2H, J=6.8 Hz), 3.92 (s, 3H), 3.89 (s, 3H), 1.45 (t, 3H, J=6.8 Hz).

Workup

  1. customIn a 20-mL capacity microwave vessel was combined
  2. customThe mixture was purged with nitrogen gas for 30 seconds
  3. customthe vessel was sealed
  4. customafter which the starting material was consumed (TLC)
  5. additionThe mixture was diluted with EtOAc (100 mL)
  6. washwashed with water (2×75 mL)
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was purified by column chromatography (SiO2, 7:3 hexanes/EtOAc)

Sources & evidence

ORD record
ord-d4c61104eba445bd8fbfda65eee28424
Source dataset
uspto-grants-2008_12
Patent number
US07470723B2

Reaction notes

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