1-Methyl-1,4-cyclohexadiene → HCID 86722319, compound

HRID 874832Notes

Reaction equation

HRID 874832 reaction equation
Cl.[CH2:2]([NH:9][CH:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1)[C:3]1[CH:8]=CC=CC=1.C(N(C(C)C)CC)(C)C.BrCCC1[O:31][CH2:30][CH2:29][O:28]1.CC1CC=CCC=1>C(#N)C.C(Cl)Cl>[O:28]1[CH2:29][CH2:30][O:31][CH:8]1[CH2:3][CH2:2][NH:9][CH:10]1[CH2:11][CH2:12][CH2:13][CH2:14]1

Participants

7

Reactant 4

HCID 780061-Methyl-1,4-cyclohexadieneHCID 81531DiisopropylethylamineHCID 877762-(2-Bromoethyl)-1,3-dioxolaneHCID 17289667HCID 17289667, compound

Product 1

HCID 86722319HCID 86722319, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a suspension of N-benzylcyclopentanamine hydrochloride (0.986 g, 4.66 mmol) in acetonitrile (10 mL) was added di-iso-propylethylamine (2.0 mL, 11.5 mmol) and the mixture stirred at room temperature for 10 minutes. A solution of 2-(2-bromoethyl)-1,3-dioxolane (1.01 g, 5.58 mmol) in acetonitrile (5 mL) was added and the mixture heated at 80° C. for 48 hours. The reaction mixture was diluted with DCM and was washed with water, dried (magnesium sulfate), filtered and the solvent evaporated at reduced pressure. The residue was loaded onto an SCX-2 cartridge and eluted with acetonitrile (4 column volumes) and then 10% triethylamine/acetonitrile (4 column volumes). The product containing fractions were combined and the solvent evaporated at reduced pressure. The residue was dissolved in ethanol (10 mL) and 10% palladium on charcoal (0.90 g) added. The mixture was stirred at room temperature for 5 minutes and then 1-methyl-1,4-cyclohexadiene (1.9 mL, 16.9 mmol) added. The reaction mixture heated to reflux and then the reaction mixture stirred under reflux for 1 hour. The reaction mixture allowed to cool and the suspension filtered. The filtrate was evaporated at reduced pressure to afford the title compound (0.249 g, 40%).

Workup

  1. temperaturethe mixture heated at 80° C. for 48 hours
  2. washwas washed with water
  3. dry with materialdried (magnesium sulfate)
  4. filtrationfiltered
  5. customthe solvent evaporated at reduced pressure
  6. washeluted with acetonitrile (4 column volumes)
  7. additionThe product containing fractions
  8. customthe solvent evaporated at reduced pressure
  9. dissolutionThe residue was dissolved in ethanol (10 mL)
  10. addition10% palladium on charcoal (0.90 g) added
  11. stirringThe mixture was stirred at room temperature for 5 minutes
  12. temperatureThe reaction mixture heated
  13. temperatureto reflux
  14. stirringthe reaction mixture stirred
  15. temperatureunder reflux for 1 hour
  16. temperatureto cool
  17. filtrationthe suspension filtered
  18. customThe filtrate was evaporated at reduced pressure

Sources & evidence

ORD record
ord-116a99361d5b449b94f0fbc06e2d87e9
Source dataset
uspto-grants-2015_03
Patent number
US08980913B2

Reaction notes

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