Methane → HCID 57941417, compound

HRID 1438013Notes

Reaction equation

HRID 1438013 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.[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Br)=[CH:26][CH:25]=1.C>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O.C(O)C>[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][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:26][CH:25]=1

Participants

7

Reactant 3

HCID 297MethaneHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 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 57941417HCID 57941417, compoundYield 48%

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-chlorobenzyl bromide (400 mg, 1.95 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 an off-white solid. This was dissolved in ethanol and the solution was treated with charcoal, then filtered through Celite and evaporated. 1H NMR indicated that there was some tetrabutylammonium iodide present. The residue was dissolved in ethyl acetate (50 mL) and the solution was washed with saturated aqueous sodium thiosulfate (25 mL), dried (magnesium sulfate), filtered, evaporated and chromatographed, eluting with 75% ethyl acetate/petroleum ether, to give (4S,7R)-1-(4-chloro-benzyl)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (100 mg, 48%). APCI(+)-MS (M+H) 429.

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 an off-white solid
  11. filtrationfiltered through Celite
  12. customevaporated
  13. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
  14. washthe solution was washed with saturated aqueous sodium thiosulfate (25 mL)
  15. dry with materialdried (magnesium sulfate)
  16. filtrationfiltered
  17. customevaporated
  18. customchromatographed
  19. washeluting with 75% ethyl acetate/petroleum ether

Sources & evidence

ORD record
ord-96ac5e36ff644c658489860c14206ddc
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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