1-(Bromomethyl)-3-fluoro-5-(trifluoromethyl)benzene → HCID 57941435, compound

HRID 1438023Notes

Reaction equation

HRID 1438023 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:25]=[C:26]([CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1)[CH2:27]Br>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O.ClCCl>[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[CH2:27][C:26]1[CH:29]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:31]=[C:24]([F:23])[CH:25]=1

Participants

6

Reactant 2

HCID 27375751-(Bromomethyl)-3-fluoro-5-(trifluoromethyl)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 57941435HCID 57941435, compoundYield 54.6%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

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; 25 mg, 0.08 mmol), tetrabutylammonium iodide (30 mg, 0.08 mmol) and 3-fluoro-5-trifluoromethyl-benzyl bromide (75 mg, 0.29 mmol) in dimethylformamide (1 mL) was heated at 100° C. overnight. The reaction mixture was diluted with dichloromethane (50 mL) and the solution was washed with water/brine (1:1; 20 mL), water (2×20 mL), sodium thiosulfate (20 mL) and brine (20 mL). The solution was dried (magnesium sulfate), filtered, concentrated and purified by chromatography, eluting with 50% ethyl acetate/petroleum ether, to give (4S,7R)-2-(2,4-difluoro-phenyl)-1-(3-fluoro-5-trifluoromethyl-benzyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (21 mg, 53%) as an off-white solid. APCI(+)-MS (M+H) 481.

Workup

  1. washthe solution was washed with water/brine (1:1; 20 mL), water (2×20 mL), sodium thiosulfate (20 mL) and brine (20 mL)
  2. dry with materialThe solution was dried (magnesium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by chromatography
  6. washeluting with 50% ethyl acetate/petroleum ether

Sources & evidence

ORD record
ord-5f864119c339434f86d142b682821f77
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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