Ethanol → HCID 57941431, compound

HRID 1438025Notes

Reaction equation

HRID 1438025 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.[F:23][C:24]([F:38])([F:37])[C:25]1[CH:26]=[C:27]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[CH2:28]Br.ClCCl.C(O)C>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[F:23][C:24]([F:37])([F:38])[C:25]1[CH:26]=[C:27]([CH:30]=[C:31]([C:33]([F:36])([F:34])[F:35])[CH:32]=1)[CH2:28][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:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[F:1]

Participants

7

Reactant 4

HCID 702EthanolHCID 6344DichloromethaneHCID 1225733,5-Bis(trifluoromethyl)benzyl 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 57941431HCID 57941431, compoundYield 73.1%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °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; 100 mg, 0.33 mmol), tetrabutylammonium iodide (120 mg, 0.32 mmol) and 3,5-bis(trifluoromethyl)benzyl bromide (240 μL, 1.3 mmol) in dimethylformamide (2 mL) was heated at 100° C. overnight. Dichloromethane (50 mL) was added and the solution was washed with 1:1 water/brine (20 mL), water (2×20 mL), aqueous sodium thiosulfate (20 mL), and brine (20 mL). The solution was dried (magnesium sulfate), filtered, evaporated, and purified by column chromatography, eluting with 45-50% ethyl acetate/petroleum ether, to give an oil. The oil was co-evaporated with ethanol, and the residue was held under high vacuum to give (4S,7R)-1-(3,5-bis-trifluoromethyl-benzyl)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (128 mg, 73%) as a white solid. APCI(+)-MS (M+H) 531.

Workup

  1. washthe solution was washed with 1:1 water/brine (20 mL), water (2×20 mL), aqueous sodium thiosulfate (20 mL), and brine (20 mL)
  2. dry with materialThe solution was dried (magnesium sulfate)
  3. filtrationfiltered
  4. customevaporated
  5. custompurified by column chromatography
  6. washeluting with 45-50% ethyl acetate/petroleum ether
  7. customto give an oil

Sources & evidence

ORD record
ord-282f0a42f2724a24a8cb19bc0041738d
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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