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

HRID 593538

Reaction equation

HRID 593538 reaction equation
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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

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].

Workup

  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)

Sources & evidence

ORD record
ord-13b0b89094ac41bc94aab690cc6479f6
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Linked notes

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