4-Fluorobenzyl bromide → HCID 57941472, compound

HRID 1438011Notes

Reaction equation

HRID 1438011 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)=[CH:26][CH:25]=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=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[CH2:28][C:27]1[CH:30]=[CH:31][C:24]([F:23])=[CH:25][CH:26]=1

Participants

5

Reactant 2

HCID 680214-Fluorobenzyl bromideHCID 57941350(4r,7s)-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 57941472HCID 57941472, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of (4R,7S)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 42; 152 mg, 0.5 mmol), tetrabutylammonium iodide (195 mg, 0.52 mmol) and 4-fluorobenzyl bromide (0.33 mL, 2.57 mmol) in dimethylformamide (1 mL) was heated at 100° C. in a sealed tube for 9 h. The solvent was evaporated and ethyl acetate was added. The solution was washed with 10% aqueous sodium thiosulfate and brine, dried (sodium sulfate), filtered, evaporated, and purified using an Analogix Intelliflash 280 system (Analogix, Inc. Burlington, Wis.) with a RS-12G silica gel column, eluting with 20-100% ethyl acetate/hexanes, to give (4R,7S)-2-(2,4-difluoro-phenyl)-1-(4-fluoro-benzyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (167 mg, 81%) as an off-white solid. ES(+)-MS (M+H) 395.

Workup

  1. customThe solvent was evaporated
  2. additionethyl acetate was added
  3. washThe solution was washed with 10% aqueous sodium thiosulfate and brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified
  8. washeluting with 20-100% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-0c75f965d21c4ecc8ba1e9900f7cad96
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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