1-(Bromomethyl)-2-(trifluoromethyl)benzene → HCID 57941473, compound

HRID 1438086Notes

Reaction equation

HRID 1438086 reaction equation
[CH2:1]([N:8]1[C:16]2[C@:15]3([CH3:20])[C:17]([CH3:19])([CH3:18])[C@@H:12]([CH2:13][CH2:14]3)[C:11]=2[C:10](=[O:21])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:22][C:23]([F:33])([F:32])[C:24]1[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=1[CH2:26]Br>CN(C)C=O>[CH2:1]([N:8]1[C:16]2[C@:15]3([CH3:20])[C:17]([CH3:18])([CH3:19])[C@@H:12]([CH2:13][CH2:14]3)[C:11]=2[C:10](=[O:21])[N:9]1[CH2:26][C:25]1[CH:28]=[CH:29][CH:30]=[CH:31][C:24]=1[C:23]([F:22])([F:32])[F:33])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 1230571-(Bromomethyl)-2-(trifluoromethyl)benzene2×HCID 57941345HCID 57941345, compound2×

Product 1

HCID 57941473HCID 57941473, compoundYield 56.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A solution of (4R,7S)-1-benzyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 49; 96 mg, 0.33 mmol) and 2-(trifluoromethyl)benzyl bromide (85 mg, 0.35 mmol) in dimethylformamide (3.4 mL) was heated at 100° C. for 24 h. A second portion of 2-(trifluoromethyl)benzyl bromide (85 mg, 0.35 mmol) was added and the mixture was heated at 110° C. overnight. The solvent was evaporated and dichloromethane (100 mL) was added. The solution was washed with saturated aqueous sodium thiosulfate (150 mL), saturated aqueous sodium hydrogen carbonate (150 mL) and brine (150 mL), dried (sodium sulfate), filtered, evaporated and purified using a Biotage 40S system, eluting with 2% methanol/dichloromethane, to give (4R,7S)-1-benzyl-7,8,8-trimethyl-2-(2-trifluoromethyl-benzyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (82 mg, 55%) as an off-white solid. APCI(+)-MS (M+H) 441.

Workup

  1. customThe solvent was evaporated
  2. additiondichloromethane (100 mL) was added
  3. washThe solution was washed with saturated aqueous sodium thiosulfate (150 mL), saturated aqueous sodium hydrogen carbonate (150 mL) and brine (150 mL)
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified
  8. washeluting with 2% methanol/dichloromethane

Sources & evidence

ORD record
ord-c61930a5798646a5be7b9b8e4b10e788
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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