Phenethyl bromide → (1R,7S)-4-(2,4-difluorophenyl)-1,10,10-trimethyl-3-(2-phenylethyl)-3,4-diazatricyclo[5.2.1.02,6]dec-2(6)-en-5-one

HRID 1437970Notes

Reaction equation

HRID 1437970 reaction equation
Br[CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[F:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=1[N:18]1[C:26](=[O:27])[C:25]2[C@@H:24]3[C:28]([CH3:30])([CH3:29])[C@@:21]([CH3:31])([CH2:22][CH2:23]3)[C:20]=2[NH:19]1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O.ClCCl>[F:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=1[N:18]1[C:26](=[O:27])[C:25]2[C@@H:24]3[C:28]([CH3:30])([CH3:29])[C@@:21]([CH3:31])([CH2:22][CH2:23]3)[C:20]=2[N:19]1[CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 2

HCID 7666Phenethyl bromide2×HCID 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 57941312(1R,7S)-4-(2,4-difluorophenyl)-1,10,10-trimethyl-3-(2-phenylethyl)-3,4-diazatricyclo[5.2.1.02,6]dec-2(6)-en-5-oneYield 28%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalyst2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (2-bromoethyl)benzene (200 μL, 1.46 mmol), (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 14; 100 mg, 0.33 mmol) and tetra-n-butylammonium iodide (94 mg, 0.25 mmol) in N,N-dimethylformamide (1 mL) was heated in a pressure tube in an oil-bath at 100° C. for 18 h. Additional portions of (2-bromoethyl)benzene (200 μL, 2.2 mmol) and tetra-n-butylammonium iodide (100 mg, 0.27 mmol) were added and the reaction mixture was heated at 100° C. for 3 days, and then allowed to stand overnight at room temperature. The reaction mixture was diluted with dichloromethane (100 mL), washed with water (5×25 mL) and sodium thiosulfate solution (25 mL), dried (magnesium sulfate), filtered, and evaporated and the residue was purified on an Isco 40 g column, eluting with 40-100% ethyl acetate/hexanes to give (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1-phenethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (37 mg, 28%) as a pale yellow oil that solidified on standing. ES(+)-MS (M+H) 409.

Workup

  1. temperaturethe reaction mixture was heated at 100° C. for 3 days
  2. washwashed with water (5×25 mL) and sodium thiosulfate solution (25 mL)
  3. dry with materialdried (magnesium sulfate)
  4. filtrationfiltered
  5. customevaporated
  6. customthe residue was purified on an Isco 40 g column
  7. washeluting with 40-100% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-c74b4edec4344129a76bc077b8af170d
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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