Water → 5-bromo-3-(N-methylpyrrolidin-3-yl)1H-indole

HRID 1604281Notes

Reaction equation

HRID 1604281 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Br:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2[CH:17]1[C:22](=O)[N:21]([CH3:24])[C:19](=O)[CH2:18]1.O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+].O>O1CCCC1.C(OCC)(=O)C>[Br:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2[CH:17]1[CH2:18][CH2:19][N:21]([CH3:24])[CH2:22]1

Participants

7

Reactant 4

HCID 962WaterHCID 62649Sodium sulfate decahydrateHCID 15326267HCID 15326267, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 153262755-bromo-3-(N-methylpyrrolidin-3-yl)1H-indoleYield 73%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of lithium aluminum hydride (1.10 g, 29.0 mmol, 2.2 eq) in anhydrous tetrahydrofuran (60 mL) at 0° C. was added 3-(5-bromoindol-3-yl)-N-methylsuccinimide (4.00 g, 13.02 mmol) portionwise cautiously. The resulting reaction mixture was heated at reflux under nitrogen for 2 hours. The reaction mixture was then cooled, and sodium sulfate decahydrate (approximately 20 g) was added slowly and cautiously, followed by the addition of water (approximately 2 mL) and ethyl acetate (200 mL). The resulting mixture was stirred at room temperature under nitrogen for 2 hours, and then filtered through Celite®. The filtrate was evaporated under reduced pressure to afford the title compound (2.64 g, 9.46 mmol, 73%) as an off-white solid: mp, 163.0-164.0° C.; TLC Rf =0.30 in 9:1:0.1 [methylene chloride/methanol/ammonium hydroxide]; 1H NMR (DMSO-d6) δ11.0 (br m, NH), 7.74 (d, J=1.3 Hz, 1H), 7.29 (d, J=8.8 Hz,1H), 7.20 (br s,1H), 7.15 (dd, J=1.7 and 8.6 Hz, 1H), 3.55-3.45 (m, 1H), 2.88 (t, J=8.2 Hz, 1H), 2.62-2.42 (m, 3H), 2.29 (s, 3H), 2.28-2.21 (m, 1H), 1.90-1.80 (m, 1H); 13C NMR (DMSO-d6) d 135.4, 128.2, 123.4, 122.9, 121.1, 118.3, 113.5, 110.8, 62.6, 56.0, 42.1, 34.4, 32.2; HMRS calculated for C13H15BrN2 278.0415, found 278.0355.

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas heated
  3. temperatureat reflux under nitrogen for 2 hours
  4. temperatureThe reaction mixture was then cooled
  5. filtrationfiltered through Celite®
  6. customThe filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-826bb73cff6b4cd69a24a2cbb6759b9e
Source dataset
uspto-grants-1999_11
Patent number
US05994352

Reaction notes

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