Benzyl Bromide → (4r,7s)-1-Benzyl-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one

HRID 1438009ノート

反応式

HRID 1438009 の反応式
[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.[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.C(O)C>[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:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[F:1])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

参加物

6

反応物 2

HCID 7498Benzyl BromideHCID 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 回

生成物 1

HCID 16116871(4r,7s)-1-Benzyl-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one収率 80%

試薬・触媒・溶媒 3

HCID 67553Tetrabutylammonium Iodide触媒HCID 702Ethanol溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

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; 213 mg, 0.7 mmol), tetrabutylammonium iodide (271 mg, 0.7 mmol) and benzyl bromide (0.45 mL, 3.7 mmol) in dimethylformamide (1.4 mL) was heated at 100° C. in a sealed tube for 24 h and then left at room temperature for a further 24 h. The solvent was evaporated and ethyl acetate was added. The solution was washed with 10% aqueous sodium thiosulfate and brine, dried (sodium sulfate), filtered, evaporated, and purified using an Analogix Intelliflash 280 system (Analogix, Inc. Burlington, Wis.) with a RS-12G silica gel column, eluting with 10-100% ethyl acetate/hexanes, to give a light brown foam. This was dissolved in ethanol and the solution was treated with activated carbon (15 mg) and heated at 50° C. for 1 h. The mixture was filtered through Celite and the Celite was washed with ethanol. The combined filtrates were evaporated and the resulting foam was dried under high vacuum to give (4R,7S)-1-benzyl-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (220 mg, 80%) as an off-white solid. ES(+)-MS (M+H) 395.

後処理

  1. customThe solvent was evaporated
  2. additionethyl acetate was added
  3. washThe solution was washed with 10% aqueous sodium thiosulfate and brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified
  8. washeluting with 10-100% ethyl acetate/hexanes
  9. customto give a light brown foam
  10. additionthe solution was treated with activated carbon (15 mg)
  11. filtrationThe mixture was filtered through Celite
  12. washthe Celite was washed with ethanol
  13. customThe combined filtrates were evaporated
  14. customthe resulting foam was dried under high vacuum

出典と根拠

ORDレコード
ord-485ef22d2858448ea0ef678cf9e5f14a
出典データセット
uspto-grants-2009_11
特許番号
US07622492B2

反応ノート

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