1,2-Dibromoethane → HCID 66920480、化合物

HRID 1510091ノート

反応式

HRID 1510091 の反応式
BrCCBr.[Cl:5][C:6]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:7]=1[CH2:8]Br.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][N:25]([C:28]([C:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[N:32]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[C:31]=2Cl)=[O:29])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN1C(=O)CCC1.[Zn].C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.[Ni+2]>[C:15]([O:19][C:20]([N:22]1[CH2:23][CH2:24][N:25]([C:28]([C:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[N:32]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[C:31]=2[CH2:8][C:7]2[CH:10]=[C:11]([F:14])[CH:12]=[CH:13][C:6]=2[Cl:5])=[O:29])[CH2:26][CH2:27]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

参加物

9

反応物 3

HCID 78391,2-DibromoethaneHCID 27736232-Chloro-5-fluorobenzyl bromideHCID 45257316HCID 45257316、化合物

生成物 1

HCID 66920480HCID 66920480、化合物収率 23.1%

試薬・触媒・溶媒 5

HCID 23994Zinc触媒HCID 67553Tetrabutylammonium Iodide触媒HCID 9834912Nickel(II) acetylacetonate触媒HCID 8028Tetrahydrofuran溶媒3 回HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
0 °C

実験手順

To a suspension of zinc (176 mg, 2.69 mmol) in dry THF (1 ml) in a dry flask under argon was added 1,2-dibromoethane (5.79 μl, 67.2 μmol). The mixture was heated three times to reflux with a heat-gun. After 5 min the flask was placed in an ice bath and a solution of 2-chloro-5-fluoro-benzylbromide (182 μl, 1.34 mmol) in dry THF (1.5 ml) was added slowly, so that the temperature remained at 0° C. The mixture was stirred at 0° C. for 3 h. Then the cooled suspension was added dropwise to a precooled solution (0° C.) of the compound of example 16, step 1 (59.0 mg, 134 μmol), nickel acetylacetonate (3.44 mg, 13.4 μmol) and tetrabutylammonium iodide (149 mg, 402 μmol) in THF (4 ml) and NMP (2 ml). The reaction mixture was stirred at 0° C. for 3 h and then at room temperature for 48 h. The mixture was quenched with water and extracted with EA. The organic layer was separated, dried over sodium sulfate, filtered, and evaporated under reduced pressure. The residue was purified by preparative HPLC. The eluate was lyophilized overnight to give 17 mg of the title compound.

後処理

  1. temperatureThe mixture was heated three times
  2. temperatureto reflux with a heat-gun
  3. customremained at 0° C
  4. stirringThe reaction mixture was stirred at 0° C. for 3 h
  5. waitat room temperature for 48 h
  6. customThe mixture was quenched with water
  7. extractionextracted with EA
  8. customThe organic layer was separated
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated under reduced pressure
  12. customThe residue was purified by preparative HPLC
  13. waitThe eluate was lyophilized overnight

出典と根拠

ORDレコード
ord-e3701d06c94c45bab2f5f48706514739
出典データセット
uspto-grants-2012_07
特許番号
US08211885B2

反応ノート

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