Methane → HCID 57941395, compound

HRID 1438014Notes

Reaction equation

HRID 1438014 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.[C:23]([C:27]1[CH:34]=[CH:33][C:30]([CH2:31]Br)=[CH:29][CH:28]=1)([CH3:26])([CH3:25])[CH3:24].C>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O.C(O)C>[C:23]([C:27]1[CH:28]=[CH:29][C:30]([CH2:31][N:10]2[C:11]3[C@@:12]4([CH3:22])[C:19]([CH3:21])([CH3:20])[C@H:15]([CH2:14][CH2:13]4)[C:16]=3[C:17](=[O:18])[N:9]2[C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])=[CH:33][CH:34]=1)([CH3:26])([CH3:24])[CH3:25]

Participants

7

Reactant 3

HCID 297MethaneHCID 878361-(Bromomethyl)-4-(1,1-dimethylethyl)benzeneHCID 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 57941395HCID 57941395, compoundYield 68.4%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °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; 150 mg, 0.49 mmol), tetrabutylammonium iodide (181 mg, 0.49 mmol) and 4-tert-butylbenzyl bromide (360 μL, 1.96 mmol) in dimethylformamide (3 mL) was heated at 80° C. for 4 days. The solvent was evaporated, dichloromethane (50 mL) was added and the solution was washed with water (2×20 mL), saturated aqueous sodium thiosulfate (20 mL), and brine (20 mL). The solution was dried (magnesium sulfate), filtered, evaporated, and purified by column chromatography, eluting with 60-70% ethyl acetate/petroleum ether, and dried under high vacuum overnight to give a pale yellow foam. This was dissolved in ethanol and treated with charcoal. The mixture was filtered through Celite, and the filtrate was evaporated and dried under high vacuum to give (4S,7R)-1-(4-tert-butyl-benzyl)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (151 mg, 68%). APCI(+)-MS (M+H) 451.

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 materialThe solution was dried (magnesium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified by column chromatography
  8. washeluting with 60-70% ethyl acetate/petroleum ether
  9. customdried under high vacuum overnight
  10. customto give a pale yellow foam
  11. filtrationThe mixture was filtered through Celite
  12. customthe filtrate was evaporated
  13. customdried under high vacuum

Sources & evidence

ORD record
ord-c937603ff5c64af1adb27be07aef319b
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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