4-Methoxybenzyl bromide → HCID 57941459, compound

HRID 1438015Notes

Reaction equation

HRID 1438015 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.[CH3:23][O:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29]Br)=[CH:27][CH:26]=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[CH2:29][C:28]1[CH:31]=[CH:32][C:25]([O:24][CH3:23])=[CH:26][CH:27]=1

Participants

5

Reactant 2

HCID 1650214-Methoxybenzyl bromideHCID 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 57941459HCID 57941459, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 14; 150 mg, 0.49 mmol), tetrabutylammonium iodide (181 mg, 0.49 mmol) and 4-methoxybenzyl bromide (280 μL, 1.94 mmol) in dimethylformamide (3 mL) was heated at 80° C. overnight. The solvent was evaporated, dichloromethane (50 mL) was added and the solution was washed with water (2×20 mL), saturated aqueous sodium thiosulfate (20 mL), and brine (20 mL). The solution was dried (magnesium sulfate), filtered, evaporated, and purified by column chromatography, eluting with 60-75% ethyl acetate/petroleum ether, and dried under high vacuum overnight to give (4S,7R)-2-(2,4-difluoro-phenyl)-1-(4-methoxy-benzyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (162 mg, 78%). APCI(+)-MS (M+H) 425.

Workup

  1. customThe solvent was evaporated
  2. additiondichloromethane (50 mL) was added
  3. washthe solution was washed with water (2×20 mL), saturated aqueous sodium thiosulfate (20 mL), and brine (20 mL)
  4. dry with materialThe solution was dried (magnesium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified by column chromatography
  8. washeluting with 60-75% ethyl acetate/petroleum ether
  9. customdried under high vacuum overnight

Sources & evidence

ORD record
ord-35962af6a2494a939eea977f88da829c
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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