Ethylene → HCID 86685976, compound

HRID 2277682Notes

Reaction equation

HRID 2277682 reaction equation
BrCCBr.C=C.[Si](Cl)(C)(C)C.Br[C:13]1[N:14]([CH3:18])[CH:15]=[CH:16][N:17]=1.Br[C:20]1[CH:21]=[C:22]([N:26]2[CH2:35][CH2:34][C:33]3[C:28](=[CH:29][CH:30]=[C:31]([Cl:36])[CH:32]=3)[C:27]2=[O:37])[CH:23]=[N:24][CH:25]=1>C1COCC1.[Zn].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.O>[Cl:36][C:31]1[CH:32]=[C:33]2[C:28](=[CH:29][CH:30]=1)[C:27](=[O:37])[N:26]([C:22]1[CH:23]=[N:24][CH:25]=[C:20]([C:13]3[N:14]([CH3:18])[CH:15]=[CH:16][N:17]=3)[CH:21]=1)[CH2:35][CH2:34]2

Participants

10

Reactant 5

HCID 6325EthyleneHCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 27732622-Bromo-1-methyl-1H-imidazoleHCID 86685975HCID 86685975, compound

Product 1

HCID 86685976HCID 86685976, compoundYield 16.2%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred suspension of zinc dust (130 mg, 1.98 mmol) in THF (2.0 mL) was added 1,2-dibromoethane (0.02 mL). The mixture was heated with a hair dryer until the evolution of ethylene gas was complete. TMS-Cl (0.02 mL) and 2-bromo-1-methyl-1H-imidazole (0.07 mL, 0.66 mmol) were then added to the above suspension and it was allowed to stir at RT for 30 minutes before the addition of 2-(5-bromo-pyridin-3-yl)-6-chloro-3,4-dihydro-2H-isoquinolin-1-one (74 mg, 0.22 mmol, example 7) and Pd(PPh3)4 (14 mg, 0.011 mmol). The resulting reaction mixture was then heated to 90° C. for 6 hours before it was poured into H2O (50 mL) and extracted with EtOAc (2×80 mL). The combined organic layers were washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give a crude product which was then purified by prep-HPLC to give title compound (12.0 mg, 16.2%) as a white foam. MS: 339.1 (M+H+).

Workup

  1. customThe resulting reaction mixture
  2. extractionextracted with EtOAc (2×80 mL)
  3. washThe combined organic layers were washed with brine
  4. customdried over anhy
  5. filtrationNa2SO4, filtered
  6. concentrationconcentrated in vacuo
  7. customto give a crude product which
  8. customwas then purified by prep-HPLC

Sources & evidence

ORD record
ord-ab3b893bec9b435e8471bd91610224bc
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

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