Methyl iodide → (4s,7r)-1,7,8,8-Tetramethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one

HRID 1437906Notes

Reaction equation

HRID 1437906 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.[CH3:21]I>CN(C)C=O>[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[N:8]2[CH3:21])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 6328Methyl iodideHCID 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 57941522(4s,7r)-1,7,8,8-Tetramethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-oneYield 55.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (4S,7R)-2-phenyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 6; 4.77 g, 17.8 mmol) and methyl iodide (2.2 mL, 35.3 mmol) in N,N-dimethylformamide (30 mL) was purged with argon and then heated in a sealed tube at 100° C. overnight. The reaction mixture was cooled to room temperature, diluted with sodium bicarbonate and extracted three times with ethyl acetate. The combined organic extracts were washed with water and brine, dried (magnesium sulfate), filtered, evaporated and purified using an Analogix Intelliflash 280 system (Analogix, Inc., Burlington, Wis.) with an Analytical Sales 120 g column, eluting with 25-75% ethyl acetate/hexanes followed by recrystallization from ethyl acetate to give (4S,7R)-2-phenyl-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (2.8 g) of white crystals. The filtrate was evaporated and recrystallized from ethyl acetate to give a further 0.53 g, and the resulting filtrate was evaporated, dissolved in dichloromethane, treated with decolorizing charcoal and crystallized from dichloromethane to give a further 0.77 g of product. The total yield was 4.1 g (82%). EI(+)-MS (M+H) 283.

Workup

  1. customwas purged with argon
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additiondiluted with sodium bicarbonate
  4. extractionextracted three times with ethyl acetate
  5. washThe combined organic extracts were washed with water and brine
  6. dry with materialdried (magnesium sulfate)
  7. filtrationfiltered
  8. customevaporated
  9. custompurified
  10. washeluting with 25-75% ethyl acetate/hexanes
  11. customfollowed by recrystallization from ethyl acetate

Sources & evidence

ORD record
ord-e14aee839a32448580f471d525ceac7e
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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