Methane → HCID 69020926, compound

HRID 1437964Notes

Reaction equation

HRID 1437964 reaction equation
[CH:1]1([CH2:7]Br)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:9]1([N:15]2[C:23](=[O:24])[C:22]3[C@@H:21]4[C:25]([CH3:27])([CH3:26])[C@@:18]([CH3:28])([CH2:19][CH2:20]4)[C:17]=3[NH:16]2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O.ClCCl.CO>[CH:1]1([CH2:7][N:16]2[C:17]3[C@:18]4([CH3:28])[C:25]([CH3:27])([CH3:26])[C@@H:21]([CH2:20][CH2:19]4)[C:22]=3[C:23](=[O:24])[N:15]2[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 3

HCID 297MethaneHCID 137636Cyclohexane, (bromomethyl)-3×HCID 57941335(4s,7r)-2-Phenyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one2×

Product 1

HCID 69020926HCID 69020926, compoundYield 4.1%

Reagents, catalysts & solvents 4

HCID 67553Tetrabutylammonium IodideCatalyst2×HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of cyclohexylmethyl bromide (2.1 mL, 15 mmol), (4R,7S)-2-phenyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 6; 395 mg, 1.47 mmol) and tetra-n-butylammonium iodide (400 mg, 1.08 mmol) in N,N-dimethylformamide (4 mL) was heated in an oil-bath at 100° C. for 64 h. Additional quantities of in N,N-dimethylformamide (2 mL), cyclohexylmethyl bromide (2.1 mL, 15 mmol), and tetra-n-butylammonium iodide (400 mg, 1.08 mmol) were added and the mixture was heated at 135° C. for 20 h. An additional quantity of cyclohexylmethyl bromide (2.1 mL, 15 mmol) was added and the mixture was heated at 135° C. for 6 days. The reaction mixture to cooled to room temperature and then diluted with dichloromethane (150 mL) and washed with water (5×30 mL), aqueous sodium thiosulfate solution (2×30 mL) and brine (30 mL). The organic extract was dried (magnesium sulfate), filtered, evaporated, and the residue purified on an Isco 40 g column, eluting with 15-100% ethyl acetate/hexanes and then held under high vacuum to give an orange gum. This was treated with charcoal in methanol in a warm water bath, and the resulting mixture was filtered, evaporated and held under high vacuum to give (4R,7S)-1-(cyclohexyl)methyl-7,8,8-trimethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (22 mg, 4%) as a yellow gum. ES(+)-MS (M+H) 365.

Workup

  1. temperaturethe mixture was heated at 135° C. for 20 h
  2. temperaturethe mixture was heated at 135° C. for 6 days
  3. temperatureThe reaction mixture to cooled to room temperature
  4. washwashed with water (5×30 mL), aqueous sodium thiosulfate solution (2×30 mL) and brine (30 mL)
  5. extractionThe organic extract
  6. dry with materialwas dried (magnesium sulfate)
  7. filtrationfiltered
  8. customevaporated
  9. customthe residue purified on an Isco 40 g column
  10. washeluting with 15-100% ethyl acetate/hexanes
  11. customto give an orange gum
  12. filtrationthe resulting mixture was filtered
  13. customevaporated

Sources & evidence

ORD record
ord-b41a4bd66e984973b93ebe92c4a69304
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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