Ethanol → HCID 16116993, compound

HRID 1438022Notes

Reaction equation

HRID 1438022 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]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:25]=1[CH2:26]Br.ClCCl.C(O)C>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[F:23][C:24]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:25]=1[CH2:26][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 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 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 16116993HCID 16116993, compoundYield 72%

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; 500 mg, 1.64 mmol), tetrabutylammonium iodide (605 mg, 1.64 mmol) and 2,4-difluorobenzyl bromide (840 μL, 6.54 mmol) in dimethylformamide (10 mL) was heated at 100° C. overnight. Dichloromethane (250 mL) was added and the solution was washed with water (3×100 mL), aqueous sodium thiosulfate (100 mL), and brine (100 mL). The solution was dried (magnesium sulfate), filtered, evaporated, and purified by column chromatography, eluting with 45-50% ethyl acetate/petroleum ether. Fractions homogeneous for the product were concentrated to give an oil which was co-evaporated with ethanol and then held under high vacuum to give (4S,7R)-1-(2,4-difluoro-benzyl)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (508 mg, 71%). APCI(+)-MS (M+H) 431.

Workup

  1. washthe solution was washed with water (3×100 mL), aqueous sodium thiosulfate (100 mL), and brine (100 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. concentrationFractions homogeneous for the product were concentrated
  8. customto give an oil which

Sources & evidence

ORD record
ord-17c062be044841d2a1205a9653d3e70b
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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