5-Nitroindole → 5-nitro-1-(2-pyrrolidin-1-ylethyl)-1H-indole

HRID 601507Notes

Reaction equation

HRID 601507 reaction equation
Cl.Cl[CH2:3][CH2:4][N:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1.[N+:10]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][CH:17]=[CH:16]2)([O-:12])=[O:11].[H-].[Na+]>CN(C=O)C.O>[N+:10]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[N:18]([CH2:3][CH2:4][N:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1)[CH:17]=[CH:16]2)([O-:12])=[O:11]

Participants

6

Reactant 3

HCID 225235-NitroindoleHCID 24758Sodium hydrideHCID 816681-(2-Chloroethyl)pyrrolidine hydrochloride

Product 1

HCID 114026955-nitro-1-(2-pyrrolidin-1-ylethyl)-1H-indoleYield 87%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Dissolve 1-(2-chloro-ethyl)-pyrrolidine hydrochloride (2.36 g, 13.9 mmol) and 5-nitro-1H-indole (1.50 g, 9.23 mmol) in DMF (25 mL) and carefully treat with sodium hydride (60% dispersion, 1.50 g, 37.5 mmol). Stir the mixture at room temperature overnight, then dilute with cold water (100 mL) and extract with EtOAc (3×50 mL). Was the combined organic portions with water (2×50 mL) and brine (50 mL). Dry, filter and concentrate under vacuum. Purify the crude material by flash chromatography, using 100% acetone as eluant, to give the title compound as a yellow oil (2.08 g, 87%). MS (ES+) 260.1 (M+1)+. 1H NMR (400 MHz, CDCl3): δ 8.57 (d, 1H, J=2.2 Hz), 8.10 (dd, 1H, J=9.2, 2.2 Hz), 7.37 (d, 1H, J=9.2 Hz), 7.30 (d, 1H, J=3.1 Hz), 6.67 (d, 1H, J=3.1 Hz), 4.29 (t, 2H, J=7.3 Hz), 2.89 (t, 2H, J=7.0 Hz), 2.54 (m, 4H), 1.78 (m, 4H).

Workup

  1. extractionextract with EtOAc (3×50 mL)
  2. customDry
  3. filtrationfilter
  4. concentrationconcentrate under vacuum
  5. customPurify the crude material by flash chromatography

Sources & evidence

ORD record
ord-f4e88f2039334357a6a88b65b7fe8519
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

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