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

HRID 1438003Notes

Reaction equation

HRID 1438003 reaction equation
[F: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.Br[CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[F: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 78911-Bromo-3-methylbutaneHCID 57941339(4s,7r)-2-(2,4-Difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one2×

Product 1

HCID 57941505(4s,7r)-2-(2,4-Difluoro-phenyl)-7,8,8-trimethyl-1-(3-methyl-butyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-oneYield 28%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 14; 600 mg, 1.97 mmol), tetrabutylammonium iodide (770 mg, 2.1 mmol) and 1-bromo-3-methyl-butane (2 mL, 16.7 mmol) in dimethylformamide (6 mL) was heated in an oil-bath at 120° C. for 18 h. The solvent was evaporated and dichloromethane (75 mL) was added. The solution was washed with water (5×20 mL) and aqueous sodium thiosulfate (20 mL), dried (magnesium sulfate), filtered, and evaporated. The residue was purified using an ISCO 40 g column, eluting with 20-90% ethyl acetate/hexanes to give (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1-(3-methyl-butyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (204 mg, 28%) as a white solid. ES(+)-MS (M+H) 375.

Workup

  1. customThe solvent was evaporated
  2. additiondichloromethane (75 mL) was added
  3. washThe solution was washed with water (5×20 mL) and aqueous sodium thiosulfate (20 mL)
  4. dry with materialdried (magnesium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified
  8. washeluting with 20-90% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-1000c879d3d64e0da30003231e24d9a7
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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