Tributylvinyltin → 6-vinyl-1H-indazole

HRID 246035

Reaction equation

HRID 246035 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][CH:3]=1.[CH2:11]([Sn](CCCC)(CCCC)C=C)[CH2:12]CC>C1(C)C=CC=CC=1.COCCOC.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:11]([C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][CH:3]=1)=[CH2:12]

Participants

7

Reactant 2

HCID 81998Tributylvinyltin2×HCID 178424716-Bromo-1H-indazole2×

Product 1

HCID 866779366-vinyl-1H-indazoleYield 79.6%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 1140TolueneSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 6-bromo-1H-indazole (600 mg, 3.05 mmol) in toluene (18 ml) and 1,2-dimethoxyethane (6 ml) were added tributyl(vinyl)tin (1.33 ml, 4.57 mmol) and PdCl2(PPh3)2 (214 mg, 0.31 mmol). The reaction was purged with argon then heated at reflux for 3 h. Additional tributyl(vinyl)tin (0.66 ml, 2.28 mmol) and PdCl2(PPh3)2 (107 mg, 0.15 mmol) were added and heating was continued for 1 h. The same reaction was performed on an additional batch of 6-bromo-1H-indazole (200 mg, 1.02 mmol) and the two crude batches were combined. The reactions were diluted with ethyl acetate, washed with water and brine, dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography with 5% to 50% EtOAc/heptane to isolate 350 mg (60%) of 6-vinyl-1H-indazole as a yellow solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.07 (s, 1H), 7.72 (d, J=8.3 Hz, 1H), 7.48 (s, 1H), 7.35 (d, J=8.3 Hz, 1H), 6.85 (dd, J=17.4, 11.0 Hz, 1H), 5.86 (d, J=17.4 Hz, 1H), 5.35 (d, J=11.0 Hz, 1H).

Workup

  1. customThe reaction was purged with argon
  2. temperaturethen heated
  3. temperatureat reflux for 3 h
  4. temperatureheating
  5. customThe same reaction
  6. washwashed with water and brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography with 5% to 50% EtOAc/heptane

Sources & evidence

ORD record
ord-8738c4ec8dc447b684710ede3a89b834
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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