1-Iodo-3-methylbutane → (4r,7s)-2-(2-Chloro-4-fluoro-phenyl)-7,8,8-trimethyl-1-(3-methyl-butyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one

HRID 1438036Notes

Reaction equation

HRID 1438036 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17](=[O:18])[C:16]2[C@H:15]3[C:19]([CH3:21])([CH3:20])[C@:12]([CH3:22])([CH2:13][CH2:14]3)[C:11]=2[NH:10]1.I[CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17](=[O:18])[C:16]2[C@H:15]3[C:19]([CH3:21])([CH3:20])[C@:12]([CH3:22])([CH2:13][CH2:14]3)[C:11]=2[N:10]1[CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27]

Participants

5

Reactant 2

HCID 109241-Iodo-3-methylbutaneHCID 57941366(4r,7s)-2-(2-Chloro-4-fluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one2×

Product 1

HCID 57941398(4r,7s)-2-(2-Chloro-4-fluoro-phenyl)-7,8,8-trimethyl-1-(3-methyl-butyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-oneYield 17%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (4R,7S)-2-(2-chloro-4-fluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 43; 150 mg, 0.47 mmol), tetrabutylammonium iodide (174 mg, 0.47 mmol) and 1-iodo-3-methylbutane (230 μL, 1.75 mmol) in dimethylformamide (3 mL) was heated at 80° C. for 4 days. The solvent was evaporated and dichloromethane (50 mL) was added. The solution was washed with water (2×20 mL), saturated aqueous sodium thiosulfate (20 mL), and brine (20 mL), dried (magnesium sulfate), filtered, concentrated, purified by chromatography, eluting with 60-80% ethyl acetate/petroleum ether, and dried under high vacuum overnight to give (4R,7S)-2-(2-chloro-4-fluoro-phenyl)-7,8,8-trimethyl-1-(3-methyl-butyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (31 mg, 17%) as a tacky oil. APCI(+)-MS (M+H) 391.

Workup

  1. customThe solvent was evaporated
  2. additiondichloromethane (50 mL) was added
  3. washThe solution was washed with water (2×20 mL), saturated aqueous sodium thiosulfate (20 mL), and brine (20 mL)
  4. dry with materialdried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by chromatography
  8. washeluting with 60-80% ethyl acetate/petroleum ether
  9. customdried under high vacuum overnight

Sources & evidence

ORD record
ord-51d19562aa604b548270daf62f9a0ec1
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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