Benzyl Bromide → HCID 15953817, compound

HRID 1437978Notes

Reaction equation

HRID 1437978 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:16](=[O:17])[C:15]2[C@H:14]3[C:18]([CH3:20])([CH3:19])[C@:11]([CH3:21])([CH2:12][CH2:13]3)[C:10]=2[NH:9]1.[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[CH2:22]([N:9]1[C:10]2[C@:11]3([CH3:21])[C:18]([CH3:20])([CH3:19])[C@@H:14]([CH2:13][CH2:12]3)[C:15]=2[C:16](=[O:17])[N:8]1[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[F:1])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 2

HCID 7498Benzyl BromideHCID 57941444HCID 57941444, compound2×

Product 1

HCID 15953817HCID 15953817, compoundYield 39.5%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of (4R,7S)-2-(2-fluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 38; 890 mg, 3.11 mmol), terabutylammonium iodide (860 mg, 2.33 mmol) and benzyl bromide (1.7 mL, 14.3 mmol) in dimethylformamide (15 mL) was heated in an oil-bath at 100° C. for 3 h. The reaction mixture was cooled to room temperature and the solvent was evaporated. Dichloromethane (100 μL) was added and the solution was washed with water (5×25 mL), aqueous sodium thiosulfate (25 mL), and brine (25 mL), dried (magnesium sulfate, filtered, and evaporated. The residue was purified using an ISCO 120 g column, eluting with 60-100% ethyl acetate/hexanes. Fractions containing the product were concentrated and then co-evaporated with ether. Petroleum ether was added and the mixture was scratched to give a solid. The solvent was evaporated and the residue was co-evaporated three times with ethanol, and then dried under high vacuum at 65° C. and then at 75° C. to give (4R,7S)-1-benzyl-2-(2-fluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (462 mg, 39%) as a pale yellow solid. ES(+)-MS (M+H) 377.

Workup

  1. customthe solvent was evaporated
  2. additionDichloromethane (100 μL) was added
  3. washthe solution was washed with water (5×25 mL), aqueous sodium thiosulfate (25 mL), and brine (25 mL)
  4. dry with materialdried (magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified
  8. washeluting with 60-100% ethyl acetate/hexanes
  9. additionFractions containing the product
  10. concentrationwere concentrated
  11. additionPetroleum ether was added
  12. customto give a solid
  13. customThe solvent was evaporated
  14. customdried under high vacuum at 65° C.

Sources & evidence

ORD record
ord-3d93a381e991433aa30d686bf6c65ac2
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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