Dichloromethane → HCID 57941514, compound

HRID 1438024Notes

Reaction equation

HRID 1438024 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.[F:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Br)=[C:26]([C:32]([F:35])([F:34])[F:33])[CH:25]=1.ClCCl>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O.C(OCC)(=O)C>[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[CH2:28][C:27]1[CH:30]=[CH:31][C:24]([F:23])=[CH:25][C:26]=1[C:32]([F:34])([F:33])[F:35]

Participants

7

Reactant 3

HCID 6344DichloromethaneHCID 27375764-Fluoro-2-(trifluoromethyl)benzyl bromideHCID 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 57941514HCID 57941514, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °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; 100 mg, 0.33 mmol), tetrabutylammonium iodide (120 mg, 0.32 mmol) and 4-fluoro-2-(trifluoromethyl)benzyl bromide (204 μL, 1.3 mmol) in dimethylformamide (2 mL) was heated at 100° C. overnight. Dichloromethane (50 mL) was added and the solution was washed with 1:1 water/brine (2×25 mL), aqueous sodium thiosulfate, water, and brine. The solution was dried (magnesium sulfate), filtered, evaporated, and purified by column chromatography, eluting with 50% ethyl acetate/petroleum ether, to give an orange oil. 1H NMR showed that this oil contained some dimethyl formamide. The oil was dissolved in ethyl acetate and the solution was washed with water (3×10 mL), dried (magnesium sulfate), filtered, evaporated, then co-evaporated with ethyl ether and dichlormethane, and held under high vacuum to give (4S,7R)-2-(2,4-difluoro-phenyl)-1-(4-fluoro-2-trifluoromethyl-benzyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (63 mg, 40%) as a pale foam. APCI(+)-MS (M+H) 481.

Workup

  1. washthe solution was washed with 1:1 water/brine (2×25 mL), aqueous sodium thiosulfate, water, and brine
  2. dry with materialThe solution was dried (magnesium sulfate)
  3. filtrationfiltered
  4. customevaporated
  5. custompurified by column chromatography
  6. washeluting with 50% ethyl acetate/petroleum ether
  7. customto give an orange oil
  8. washthe solution was washed with water (3×10 mL)
  9. dry with materialdried (magnesium sulfate)
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-5fcd35cc4f7a4fa99a8859d239304dcc
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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