Dichloromethane → HCID 57941429, compound

HRID 1437975Notes

Reaction equation

HRID 1437975 reaction equation
[C:1]1([N:7]2[C:15](=[O:16])[C:14]3[C@@H:13]4[C:17]([CH3:19])([CH3:18])[C@@:10]([CH3:20])([CH2:11][CH2:12]4)[C:9]=3[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.ClCCl>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[CH3:20][C@@:10]12[C:17]([CH3:19])([CH3:18])[C@@H:13]([C:14]3[C:15](=[O:16])[N:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[N:8]([CH2:22][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[C:9]=31)[CH2:12][CH2:11]2

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 7666Phenethyl bromideHCID 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 57941429HCID 57941429, compoundYield 14.4%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (4S,7R)-7,8,8-trimethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 6; 150 mg, 0.56 mmol), tetrabutylammonium iodide (200 mg, 0.54 mmol) and (2-bromoethyl)benzene (500 μL, 3.7 mmol) in dimethylformamide (1.5 mL) was heated in a pressure tube in an oil-bath at 100° C. for 2 days. Dichloromethane (100 mL) was added and the solution was washed with water (4×25 mL) and aqueous sodium thiosulfate (25 mL), dried (magnesium sulfate), filtered, evaporated and purified using an ISCO 40 g column, eluting with 60-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated and co-evaporated successively with dichloromethane/petroleum ether and then methanol, and dried under high vacuum over the weekend at room temperature and then at 80° C. for 4 h. The residue was treated with petroleum ether to give a solid. The solvent was evaporated and the solid was dried overnight at 70° C. to give (4S,7R)-7,8,8-trimethyl-1-phenethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (30 mg, 14%) as a pale yellow solid. ES(+)-MS (M+H) 373.

Workup

  1. washthe solution was washed with water (4×25 mL) and aqueous sodium thiosulfate (25 mL)
  2. dry with materialdried (magnesium sulfate)
  3. filtrationfiltered
  4. customevaporated
  5. custompurified
  6. washeluting with 60-100% ethyl acetate/hexanes
  7. customFractions homogeneous for the product were evaporated and co-evaporated successively with dichloromethane/petroleum ether
  8. dry with materialmethanol, and dried under high vacuum over the weekend at room temperature
  9. additionThe residue was treated with petroleum ether
  10. customto give a solid
  11. customThe solvent was evaporated
  12. customthe solid was dried overnight at 70° C.

Sources & evidence

ORD record
ord-76a9b3cd67bd4aafa666df169f0927cb
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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