Sulfuryl chloride → Ethyl 4-chloro-5-hydroxy-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylate

HRID 2101821ノート

反応式

HRID 2101821 の反応式
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:5]2.S(Cl)([Cl:24])(=O)=O>C1(C)C=CC=CC=1.C(N)(C)(C)C.S(Cl)(Cl)(=O)=O>[Cl:24][C:3]1[C:2]([OH:1])=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[C:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[N:7]2[CH2:11][C:12]([F:15])([F:13])[F:14]

参加物

6

反応物 2

HCID 24648Sulfuryl chloride2 回HCID 24985291Ethyl 5-hydroxy-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylate

生成物 1

HCID 57800334Ethyl 4-chloro-5-hydroxy-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylate収率 92%

試薬・触媒・溶媒 3

HCID 6385Tert-Butylamine触媒3 回HCID 24648Sulfuryl chloride触媒HCID 1140Toluene溶媒2 回

実験手順

To a solution of ethyl 5-hydroxy-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylate (0.7 g, 2.44 mmol) in toluene (30 mL) was added tert-butyl amine (0.014 g, 0.2 mmol) and the mixture was set in an oil bath preheated at 70° C. After 1 min, a solution of sulfuryl chloride (0.37 g, 2.49 mmol) in toluene (1 mL) was added. The reaction was followed by TLC (60% CH2Cl2-hexanes) and additional reagents were added accordingly. After 30 min, more tert-butylamine (0.014 g, 0.2 mmol) and sulfuryl chloride (0.06 g, 0.37 mmol) were added. After another 30 min additional tert-butylamine (0.014 g, 0.2 mmol) and sulfuryl chloride (0.019 g, 0.12 mmol) were added and heating was continued for 30 min. Upon cooling, the mixture was partitioned between EtOAc and 0.2N HCl. The organic phase was washed with 0.2N HCl and sat'd brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (10-80% CH2Cl2-hexanes gradient) to afford the title compound (0.72 g, 92% yield, 95% purity): MS (ES) m/z 322 (M+1).

後処理

  1. customthe mixture was set in an oil bath
  2. custompreheated at 70° C
  3. additionwere added accordingly
  4. waitAfter 30 min
  5. temperatureheating
  6. waitwas continued for 30 min
  7. temperatureUpon cooling
  8. customthe mixture was partitioned between EtOAc and 0.2N HCl
  9. washThe organic phase was washed with 0.2N HCl
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash chromatography (10-80% CH2Cl2-hexanes gradient)

出典と根拠

ORDレコード
ord-f71b991cc14c409a8dc4307b2cf7f134
出典データセット
uspto-grants-2009_08
特許番号
US07572820B2

反応ノート

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