Benzyl Bromide → (4r,7s)-1-Benzyl-2-(2-chloro-4-fluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one

HRID 1438038Notes

Reaction equation

HRID 1438038 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.[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[CH2:23]([N:10]1[C:11]2[C@:12]3([CH3:22])[C:19]([CH3:21])([CH3:20])[C@@H:15]([CH2:14][CH2:13]3)[C:16]=2[C:17](=[O:18])[N:9]1[C:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[Cl:1])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

5

Reactant 2

HCID 7498Benzyl BromideHCID 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 57941427(4r,7s)-1-Benzyl-2-(2-chloro-4-fluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-oneYield 47.6%

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 benzyl bromide (223 μL, 1.9 mmol) in dimethylformamide (3 mL) was heated at 80° C. overnight and then stirred at room temperature over the weekend. 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 60-70% ethyl acetate/petroleum ether, and dried under high vacuum overnight to give (4R,7S)-1-benzyl-2-(2-chloro-4-fluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (92 mg, 38%) as a light tan solid. APCI(+)-MS (M+H) 411.

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 60-70% ethyl acetate/petroleum ether
  9. customdried under high vacuum overnight

Sources & evidence

ORD record
ord-1bd049b941b74cae843b12809cc6d6d6
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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