Sodium Iodide → HCID 16116872, compound

HRID 1438021Notes

Reaction equation

HRID 1438021 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.[I-].[Na+].[F:25][C:26]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:27]=1[CH2:28]Br.C(OCC)(=O)C>CN(C)C=O>[F:25][C:26]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:27]=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

6

Reactant 4

HCID 5238Sodium IodideHCID 8857Ethyl AcetateHCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 57941350(4r,7s)-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 16116872HCID 16116872, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (4R,7S)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 42; 101 mg, 0.33 mmol), sodium iodide (53 mg, 0.35 mmol) and 2,4-difluorobenzyl bromide (0.22 mL, 1.68 mmol) in dimethylformamide (0.8 mL) was heated under microwave irradiation at 150° C. for 1 h. Ethyl acetate was added and the solution was washed with 10% aqueous sodium thiosulfate (three times), dried (sodium sulfate), filtered, evaporated, and purified on an RS-4g silica gel column, eluting with 20-100% ethyl acetate/hexanes to give (4R,7S)-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 (82 mg, 58%) as a light brown foam. ES(+)-MS (M+H) 431.

Workup

  1. washthe solution was washed with 10% aqueous sodium thiosulfate (three times)
  2. dry with materialdried (sodium sulfate)
  3. filtrationfiltered
  4. customevaporated
  5. custompurified on an RS-4g silica gel column
  6. washeluting with 20-100% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-ae8c8c33083346f996d14abb7e641d62
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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