Methyl iodide → 3-iodo-1,5,5-trimethyl-4,5,6,7-tetrahydro-1H-indazole

HRID 245815ノート

反応式

HRID 245815 の反応式
[I:1][C:2]1[C:10]2[CH2:9][C:8]([CH3:12])([CH3:11])[CH2:7][CH2:6][C:5]=2[NH:4][N:3]=1.[CH3:13]C(C)([O-])C.[K+].CI>C1COCC1>[I:1][C:2]1[C:10]2[CH2:9][C:8]([CH3:12])([CH3:11])[CH2:7][CH2:6][C:5]=2[N:4]([CH3:13])[N:3]=1

参加物

5

反応物 3

HCID 6328Methyl iodideHCID 23665647Potassium tert-butoxideHCID 712802653-iodo-5,5-dimethyl-4,5,6,7-tetrahydro-1H-indazole

生成物 1

HCID 712801343-iodo-1,5,5-trimethyl-4,5,6,7-tetrahydro-1H-indazole収率 74%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

In a round-bottomed flask, 3-iodo-5,5-dimethyl-4,5,6,7-tetrahydro-1H-indazole (642 mg, 2.33 mmol) was dissolved in THF (8.5 ml). The solution was cooled to 0° C. and potassium tert-butoxide (365 mg, 3.26 mmol) was added. The reaction mixture was stirred at 0° C. for 40 min then methyl iodide (0.18 ml, 2.88 mmol) was added dropwise. The reaction mixture was warmed to room temperature and stirred for 1.5 h then quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/Hexanes (gradient 0-15% EtOAc) to provide 497 mg (74%) of 3-iodo-1,5,5-trimethyl-4,5,6,7-tetrahydro-1H-indazole as a white solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 3.76 (s, 3H), 2.53 (t, J=6.4 Hz, 2H), 2.11 (s, 2H), 1.58 (t, J=6.6 Hz, 2H), 0.99 (s, 6H).

後処理

  1. temperatureThe reaction mixture was warmed to room temperature
  2. stirringstirred for 1.5 h
  3. customthen quenched with water
  4. extractionextracted with EtOAc (2×)
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialthen dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was chromatographed over silica gel with EtOAc/Hexanes (gradient 0-15% EtOAc)

出典と根拠

ORDレコード
ord-3f2cbe88a32f4fcfada3140a01565d1a
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

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