Diethyl Ether → (4s,7r)-2-(3,5-Dichloro-phenyl)-1-ethyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one

HRID 1438063Notes

Reaction equation

HRID 1438063 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:17](=[O:18])[C:16]3[C@@H:15]4[C:19]([CH3:21])([CH3:20])[C@@:12]([CH3:22])([CH2:13][CH2:14]4)[C:11]=3[NH:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.I[CH2:24][CH3:25].CCOCC>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:17](=[O:18])[C:16]3[C@@H:15]4[C:19]([CH3:21])([CH3:20])[C@@:12]([CH3:22])([CH2:13][CH2:14]4)[C:11]=3[N:10]2[CH2:24][CH3:25])[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 6340Iodoethane2×HCID 57941373(4s,7r)-2-(3,5-Dichloro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one2×

Product 1

HCID 57941425(4s,7r)-2-(3,5-Dichloro-phenyl)-1-ethyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-oneYield 7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of (4S,7R)-2-(3,5-dichloro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 45; 400 mg, 1.2 mmol) and iodoethane (480 μL, 5.95 mmol) in dimethylformamide (5 mL) was heated at 95° C. for 7 h and then a further portion of iodoethane (480 μL, 5.95 mmol) was added. The solution was heated at 95° C. overnight. The solvent was evaporated, dichloromethane (100 mL) was added and the solution was washed with water (3×50 mL), saturated aqueous sodium thiosulfate (50 mL), and brine (50 mL). The solution was dried (magnesium sulfate), filtered, evaporated, and purified by column chromatography, eluting with 20% ethyl acetate/petroleum ether, and dried under high vacuum over the weekend to give a pale orange solid. The solid was stirred in a small amount of ether, and the insoluble material was filtered off and dried under high vacuum overnight to give (4S,7R)-2-(3,5-dichloro-phenyl)-1-ethyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (30 mg, 7%). ES(+)-MS (M+H) 351.

Workup

  1. temperatureThe solution was heated at 95° C. overnight
  2. customThe solvent was evaporated
  3. additiondichloromethane (100 mL) was added
  4. washthe solution was washed with water (3×50 mL), saturated aqueous sodium thiosulfate (50 mL), and brine (50 mL)
  5. dry with materialThe solution was dried (magnesium sulfate)
  6. filtrationfiltered
  7. customevaporated
  8. custompurified by column chromatography
  9. washeluting with 20% ethyl acetate/petroleum ether
  10. customdried under high vacuum over the weekend
  11. customto give a pale orange solid
  12. filtrationthe insoluble material was filtered off
  13. customdried under high vacuum overnight

Sources & evidence

ORD record
ord-2a94795d818b4e67aa43d2f46d0747dc
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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