Sodium Hydroxide → Ammonium Hydroxide

HRID 1901555Notes

Reaction equation

HRID 1901555 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C([O:14]C([N:17]1CCCC1CC1C2C(=CC=CC=2)NC=1)=O)C1C=CC=CC=1.C(O[C:40]([N:42]1[CH2:47][CH2:46][CH2:45][CH2:44][CH:43]1[CH2:48][C:49]1[C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[NH:51][CH:50]=1)=O)C1C=CC=CC=1.[OH-].[Na+]>O1CCCC1.O>[OH-:14].[NH4+:17].[CH3:40][N:42]1[CH2:47][CH2:46][CH2:45][CH:43]1[CH2:48][C:49]1[C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[NH:51][CH:50]=1.[CH3:40][N:42]1[CH2:47][CH2:46][CH2:45][CH2:44][CH:43]1[CH2:48][C:49]1[C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[NH:51][CH:50]=1

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 120500533-(N-benzyloxycarbonylpyrrolidin-2-ylmethyl)-1H-indoleHCID 199702443-(N-benzyloxycarbonylpiperid-2-ylmethyl)-1H-indoleHCID 21226445Aluminium lithium hydride

Product 3

HCID 14923Ammonium HydroxideHCID 58967Indole, 3-(1-methyl-2-piperidylmethyl)-HCID 538704423-(N-methylpyrrolidin-2-ylmethyl)-1H-indole

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
25 °C

Procedure

To a stirred mixture of lithium aluminum hydride (0.152 g, 4.00 mmol, 2 eq) in anhydrous tetrahydrofuran (10 mL) at 0° C. was added rapidly a solution of the 3-(N-benzyloxycarbonylpyrrolidin-2-ylmethyl)-1H-indole or the 3-(N-benzyloxycarbonylpiperid-2-ylmethyl)-1H-indole (2.00 mmol) in anhydrous tetrahydrofuran (5 mL). The resulting mixture is heated at reflux under a nitrogen atmosphere for 3 hours. The reaction mixture is cooled, and water (0.25 mL), 15% aqueous sodium hydroxide (0.25 mL), and then more water (0.75 mL) were added sequentially. The resulting mixture was stirred at 25° C. for 30 minutes, filtered, and the filtrate was evaporated under reduced pressure. The residue was column chromatographed using silica gel (approximately 50 g) and elution with a solution methylene chloride:methanol:ammonium hydroxide [9:1:0.1] or other appropriate solvent system to afford the corresponding 3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole or 3-(N-methylpiperid-2-ylmethyl)-1H-indole.

Workup

  1. temperatureThe resulting mixture is heated
  2. temperatureat reflux under a nitrogen atmosphere for 3 hours
  3. temperatureThe reaction mixture is cooled
  4. filtrationfiltered
  5. customthe filtrate was evaporated under reduced pressure
  6. customchromatographed
  7. washsilica gel (approximately 50 g) and elution with a solution methylene chloride

Sources & evidence

ORD record
ord-4ad7c7beff374b29bb3f63d527f19b84
Source dataset
uspto-grants-1996_11
Patent number
US05578612

Reaction notes

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