Hydrochloric Acid → 2-(5-Chloro-3-methyl-2-pyridin-3-yl-indol-1-yl)-ethanol

HRID 593538

反応式

HRID 593538 の反応式
Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)=[C:6]2[CH3:18].C[Si]([N-][Si](C)(C)C)(C)C.[K+].Cl[CH2:30][CH2:31][O:32][Si](C)(C)C.Cl>C1COCC1>[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:30][CH2:31][OH:32])[C:7]([C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)=[C:6]2[CH3:18]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 2628232-ChloroethoxytrimethylsilaneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 445539625-chloro-3-methyl-2-pyridin-3-yl-1H-indole hydrochloride

生成物 1

HCID 582157292-(5-Chloro-3-methyl-2-pyridin-3-yl-indol-1-yl)-ethanol

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

A flask is charged with 5-chloro-3-methyl-2-pyridin-3-yl-1H-indole hydrochloride (Example 2, 1.0 g, 3.58 mmol) and THF (20 mL) and cooled to 0° C. KHMDS (0.5 M in toluene, 17.9 mL, 8.95 mmol) is added and the mixture is stirred at room temperature for 30 min, followed by addition of (2-chloro-ethoxy)-trimethylsilane (1.06 mL, 8.95 mmol). The reaction mixture is stirred for 48 h at 60° C. After cooling to room temperature, aqueous 1M HCl (30 mL) is added and the mixture is stirred at room temperature for 30 min, then washed with water and extracted with ethyl acetate twice. The organic layer is dried over sodium sulfate and concentrated in vacuo. The residue is purified by silica gel flash chromatography (heptane-ethyl acetate, 1:4) to afford 2-(5-chloro-3-methyl-2-pyridin-3-yl-indol-1-yl)-ethanol as a solid. 1H NMR (400 MHz, MeOD) δ ppm 2.22 (s, 3H), 3.69 (t, J=5.9 Hz, 2H), 4.18 (t, J=5.8 Hz, 2H), 7.21 (dd, J=8.6, 2.0 Hz, 1H), 7.47 (d, J=8.6 Hz, 1H), 7.57 (d, J=1.8 Hz, 1H), 7.61-7.67 (m, 1H), 8.01 (dt, J=7.9, 2.0 Hz, 1H), 8.61-8.71 (m, 2H). HRMS (ESI) m/z 287.0953 [(M+H)+ Calcd for C16H16ClN2O: 287.0951].

後処理

  1. stirringThe reaction mixture is stirred for 48 h at 60° C
  2. temperatureAfter cooling to room temperature
  3. stirringthe mixture is stirred at room temperature for 30 min
  4. washwashed with water
  5. extractionextracted with ethyl acetate twice
  6. dry with materialThe organic layer is dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by silica gel flash chromatography (heptane-ethyl acetate, 1:4)

出典と根拠

ORDレコード
ord-13b0b89094ac41bc94aab690cc6479f6
出典データセット
uspto-grants-2016_01
特許番号
US09242963B2

関連ノート

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