Water → HCID 57941466, compound

HRID 1438010Notes

Reaction equation

HRID 1438010 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][CH:29]=[CH:28][C:25]=1[CH2:26]Br.ClCCl.O>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O.[Cl-].[Na+].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[CH2:26][C:25]1[CH:28]=[CH:29][CH:30]=[CH:31][C:24]=1[F:23]

Participants

8

Reactant 4

HCID 962WaterHCID 6344DichloromethaneHCID 67968alpha-Bromo-o-fluorotolueneHCID 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 57941466HCID 57941466, compoundYield 78%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

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 (85 mg, 0.23 mmol) and 2-fluoro-benzyl bromide (164 μL, 1.3 mmol) in dimethylformamide (2 mL) was heated at 100° C. overnight. Dichloromethane (50 mL) and a mixture of water (13 mL) and brine (6 mL) were added. The organic layer was washed with 10% aqueous sodium thiosulfate (20 μL), and brine (20 mL). The solution was dried (magnesium sulfate), filtered, evaporated, and purified by column chromatography, eluting with 50-60% ethyl acetate/petroleum ether, to give (4S,7R)-2-(2,4-difluoro-phenyl)-1-(2-fluoro-benzyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (106 mg, 78%) as a pale solid. ES(+)-MS (M+H) 413.

Workup

  1. additionwere added
  2. washThe organic layer was washed with 10% aqueous sodium thiosulfate (20 μL), and brine (20 mL)
  3. dry with materialThe solution was dried (magnesium sulfate)
  4. filtrationfiltered
  5. customevaporated
  6. custompurified by column chromatography
  7. washeluting with 50-60% ethyl acetate/petroleum ether

Sources & evidence

ORD record
ord-375fbb9813d94ee0aa1f6bceeb1baebf
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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