1-Iodo-3-methylbutane → (4s,7r)-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 1438037Notes

Reaction equation

HRID 1438037 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]>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

4

Reactant 2

HCID 109241-Iodo-3-methylbutaneHCID 57941321(4s,7r)-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 57941418(4s,7r)-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 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (4S,7R)-2-(2-chloro-4-fluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 21; 200 mg, 0.62 mmol) and 1-iodo-3-methylbutane (410 μL, 3.1 mmol) in dimethylformamide (4 mL) was heated at 100° 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 65% ethyl acetate/petroleum ether, and dried under high vacuum over the weekend to give (4S,7R)-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 (91 mg, 38%) as an off-white solid. 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 65% ethyl acetate/petroleum ether
  9. customdried under high vacuum over the weekend

Sources & evidence

ORD record
ord-e8d044e72eef4591a891a1ab1b78c909
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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