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

HRID 593538

반응식

HRID 593538 반응식
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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
0 °C

실험 절차

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].

후처리

  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)

출처 및 근거

ORD 기록
ord-13b0b89094ac41bc94aab690cc6479f6
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242963B2

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