Aluminium lithium hydride → 7-benzyloxy-3-(2-aminopropyl)-1H-indole

HRID 1072592Notes

Reaction equation

HRID 1072592 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([O:14][C:15]1[CH:16]=[CH:17][CH:18]=[C:19]2[C:23]=1[NH:22][CH:21]=[C:20]2[CH:24]=[C:25]([N+:27]([O-])=O)[CH3:26])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>O1CCCC1>[CH2:7]([O:14][C:15]1[CH:16]=[CH:17][CH:18]=[C:19]2[C:23]=1[NH:22][CH:21]=[C:20]2[CH2:24][CH:25]([NH2:27])[CH3:26])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydride2×HCID 695179147-benzyloxy-3-(2-nitroprop-1-enyl)-1H-indole

Product 1

HCID 111501987-benzyloxy-3-(2-aminopropyl)-1H-indole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
30 °C

Procedure

Lithium aluminum hydride (LAH, 24 g, 600 mmol) is added portionwise to dry tetrahydrofuran (1800 mL) at −5° C. to 5° C. A solution of the nitroolefin from above (61.6 g, 200 mmol) in tetrahydrofuran (1200 mL) is added to the LAH solution over 30 minutes while maintaining the temperature at −5° C. to 5° C. When the addition is complete, the reaction mixture is allowed to warm to 30° C. over 1.5 hours and is stirred at 25° C. to 35° C. for 2 hours. To complete the reaction, the mixture is heated to 60° C. for 30 minutes. After cooling to 0° C., the reaction is quenched by the sequential addition of water (30 mL), 5 N NaOH (30 mL), and water (100 mL) and the resulting mixture is stirred over the weekend. The aluminum salts are removed by filtration and the cake rinsed with tetrahydrofuran (500 mL). The combined filtrates are concentrated to give 47.6 g (55% purity corrected yield, approx 65% pure) of 7-benzyloxy-3-(2-aminopropyl)-1H-indole.

Workup

  1. temperaturewhile maintaining the temperature at −5° C. to 5° C
  2. additionWhen the addition
  3. customthe reaction
  4. temperaturethe mixture is heated to 60° C. for 30 minutes
  5. temperatureAfter cooling to 0° C.
  6. customthe reaction is quenched by the sequential addition of water (30 mL), 5 N NaOH (30 mL), and water (100 mL)
  7. stirringthe resulting mixture is stirred over the weekend
  8. customThe aluminum salts are removed by filtration
  9. washthe cake rinsed with tetrahydrofuran (500 mL)
  10. concentrationThe combined filtrates are concentrated

Sources & evidence

ORD record
ord-7fdc4570f28948dda1f36193437ec681
Source dataset
uspto-grants-2005_06
Patent number
US06911463B2

Reaction notes

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