Butyl vinyl ether → HCID 53683605, compound

HRID 1968657Notes

Reaction equation

HRID 1968657 reaction equation
C([Li])(C)(C)C.[CH:6]([O:8][CH2:9][CH2:10][CH2:11][CH3:12])=[CH2:7].[Cl:13][C:14]1[N:15]=[N:16][C:17](Cl)=[CH:18][CH:19]=1>CCCCC.C1COCC1.CCOC(C)=O.[Cl-].[Zn+2].[Cl-].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]>[CH2:9]([O:8][C:6]([C:17]1[N:16]=[N:15][C:14]([Cl:13])=[CH:19][CH:18]=1)=[CH2:7])[CH2:10][CH2:11][CH3:12]

Participants

9

Reactant 3

HCID 8108Butyl vinyl ether2×HCID 673313,6-DichloropyridazineHCID 178418306HCID 178418306, compound

Product 1

HCID 53683605HCID 53683605, compound

Reagents, catalysts & solvents 5

HCID 3007855ZincchlorideCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-30 °C

Procedure

THF (24.0 mL) was added rapidly dropwise to tert-butyllithium (150 mL of a 1.7 M solution in pentane) at −78° C. After 15 min, n-butyl vinyl ether (14.0 mL, 109.4 mmol) was added, and the resulting mixture was warmed to −30° C., at which point modest gas evolution was observed. As gas evolution ceased, a second portion of n-butyl vinyl ether (14.0 mL, 109.4 mmol) was added, maintaining the reaction temperature at −30° C. After gas evolution had ceased, the reaction mixture was cooled to −78° C., and a solution of zinc chloride (29.8 g, 219 mmol) in THF (250 mL) was added rapidly dropwise. After 15 min, the reaction was warmed to −10° C. and transferred via cannula to a stirred solution of 3,6-dichloropyridazine (32.6 g, 219 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (16.0 g, 21.9 mmol) in THF (200 mL) at 0° C. After 1 h at 0° C., the reaction mixture was diluted with EtOAc and filtered through a short column of CELITE®, eluting with EtOAc. The filtrate was washed with water and brine, dried (sodium sulfate), and concentrated in vacuo. The crude residue was purified by flash chromatography on silica gel (gradient elution; 0%-15% EtOAc/hexanes as eluent) to afford the title compound i-5a. 1HNMR (500 MHz, CDCl3): δ 7.80 (d, 1H, J=8.9 Hz), 7.52 (d, 1H, J=8.9 Hz), 5.76 (d, 1H, J=2.5 Hz), 4.55 (d, 1H, J=2.5 Hz), 3.97 (t, 2H, J=6.4 Hz), 1.83 (m, 2H), 1.57 (m, 2H), 1.02 (t, 3H, J=7.5 Hz).

Workup

  1. temperaturemaintaining the reaction temperature at −30° C
  2. temperaturethe reaction mixture was cooled to −78° C.
  3. waitAfter 15 min
  4. temperaturethe reaction was warmed to −10° C.
  5. waitAfter 1 h at 0° C.
  6. filtrationfiltered through a short column of CELITE®
  7. washeluting with EtOAc
  8. washThe filtrate was washed with water and brine
  9. dry with materialdried (sodium sulfate)
  10. concentrationconcentrated in vacuo
  11. customThe crude residue was purified by flash chromatography on silica gel (gradient elution; 0%-15% EtOAc/hexanes as eluent)

Sources & evidence

ORD record
ord-2b6003dd8c1b437f8abd3f460d45dadb
Source dataset
uspto-grants-2013_04
Patent number
US08426413B2

Reaction notes

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