Dimethyl Sulfoxide → ethyl 2-(1-oxo-6-vinylphthalazin-2(1H)-yl)acetate

HRID 587702Notes

Reaction equation

HRID 587702 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[NH:8][N:7]=[CH:6]2)=[CH2:2].BrC1C=C2[C:22](=CC=1)[C:21](=[O:25])NN=C2.[C:26]([O-:29])([O-])=O.[K+].[K+].[CH3:32]S(C)=O>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]>[O:13]=[C:9]1[C:10]2[C:5](=[CH:4][C:3]([CH:1]=[CH2:2])=[CH:12][CH:11]=2)[CH:6]=[N:7][N:8]1[CH2:32][C:26]([O:25][CH2:21][CH3:22])=[O:29]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 115359186-Bromophthalazin-1(2h)-oneHCID 866751746-vinylphthalazine-1(2H)-one

Product 1

HCID 86675173ethyl 2-(1-oxo-6-vinylphthalazin-2(1H)-yl)acetateYield 63%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
80 °C

Procedure

6-Vinylphthalazine-1(2H)-one (BI27): A solution of 6-bromophthalazine-1(2H)-one (0.25 g, 1.11 mmol), potassium vinyl trifluoroborate (0.446 g, 3.33 mmol) and K2CO3 (0.46 g, 3.33 mmol) in DMSO (2 mL) was degassed with argon for 20 min at ambient temperature. PdCl2(dppf) (0.04 g, 0.055 mmol) was added at ambient temperature, and the reaction mixture was heated to 80° C. for 2 h. The reaction mixture was cooled to ambient temperature and filtered through Celite® bed under vacuum and washed with EtOAc. The reaction mixture was extracted with EtOAc and the combined EtOAc layer dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; 50% EtOAc/petroleum ether) to afford the title compound as a brown solid (0.12 g, 63%): 1H NMR (400 MHz, DMSO-d6) δ 13.61 (br, 1H), 8.33 (m, 1H), 8.19 (m, 1H), 8.01 (m, 2H), 6.97 (m, 1H), 6.15 (m, 1H), 5.56 (d, J=10.8 Hz, 1H); ESIMS m/z 172.93 ([M+H]+); IR (thin film) 1748, 1655, 3241 cm−1.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. filtrationfiltered through Celite® bed under vacuum
  3. washwashed with EtOAc
  4. extractionThe reaction mixture was extracted with EtOAc
  5. dry with materialthe combined EtOAc layer dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto afford the crude product
  8. customThe crude compound was purified by column chromatography (SiO2, 100-200 mesh; 50% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-32552d9005bf486d94f1332cb99af3e9
Source dataset
uspto-grants-2016_01
Patent number
US09226501B2

Reaction notes

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