Benzyl Bromide → HCID 57941527, compound

HRID 1437994Notes

Reaction equation

HRID 1437994 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:17](=[O:18])[C:16]3[C@@H:15]4[C:19]([CH3:21])([CH3:20])[C@@:12]([CH3:22])([CH2:13][CH2:14]4)[C:11]=3[NH:10]2)=[CH:5][CH:4]=1.[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O.ClCCl>[CH2:23]([N:10]1[C:11]2[C@@:12]3([CH3:22])[C:19]([CH3:21])([CH3:20])[C@H:15]([CH2:14][CH2:13]3)[C:16]=2[C:17](=[O:18])[N:9]1[C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 2

HCID 7498Benzyl BromideHCID 57941426HCID 57941426, compound2×

Product 1

HCID 57941527HCID 57941527, compoundYield 14%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalyst2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (4S,7R)-2-(4-methoxy-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 40; 300 mg, 1.0 mmol), tetrabutylammonium iodide (371 mg, 1.0 mmol) and benzyl bromide (478 μL, 4.0 mmol) in dimethylformamide (10 mL) was heated at ˜100° C. overnight. The solvent was evaporated. Dichloromethane (150 mL) was added and the solution was washed with brine (150 mL), saturated aqueous sodium thiosulfate (150 mL; 50% w/v), saturated aqueous sodium hydrogen carbonate (150 mL) and brine (150 mL). The solution was dried (sodium sulfate), filtered, evaporated, and purified using a Biotage 40S system, eluting with 0.5-2% methanol/dichloromethane to give a partially purified product that still contained some tetrabutylammonium iodide (according to 1H NMR). The solid was dissolved in dichloromethane, washed with saturated sodium thiosulfate and brine, and then evaporated to dryness. The solid was passed through a plug of silica, eluting with 0-5% methanol/dichloromethane, to give (4S,7R)-1-Benzyl-2-(4-methoxy-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (54.5 mg, 14%). APCI(+)-MS (M+H) 389.

Workup

  1. customThe solvent was evaporated
  2. additionDichloromethane (150 mL) was added
  3. washthe solution was washed with brine (150 mL), saturated aqueous sodium thiosulfate (150 mL; 50% w/v), saturated aqueous sodium hydrogen carbonate (150 mL) and brine (150 mL)
  4. dry with materialThe solution was dried (sodium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified
  8. washeluting with 0.5-2% methanol/dichloromethane
  9. customto give a partially purified product that
  10. washwashed with saturated sodium thiosulfate and brine
  11. customevaporated to dryness
  12. washeluting with 0-5% methanol/dichloromethane

Sources & evidence

ORD record
ord-53c3d9fe2c6645aab52f7a52a6b433bf
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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