Aluminium lithium hydride → HCID 23624258, compound

HRID 1436995Notes

Reaction equation

HRID 1436995 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]3[CH2:16][C:15](=O)[NH:14][CH2:13][C:12]4[CH:18]=[CH:19][CH:20]=[CH:21][C:11]3=4)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]3[CH2:16][CH2:15][NH:14][CH2:13][C:12]4[CH:18]=[CH:19][CH:20]=[CH:21][C:11]3=4)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 24887406HCID 24887406, compound

Product 1

HCID 23624258HCID 23624258, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To an ice-water bath cooled suspension of 5-(1H-indol-5-yl)-1,2,4,5-tetrahydro-benzo[c]azepin-3-one (0.50 g, 1.8 mmol) in tetrahydrofuran (75 mL) was added lithium aluminum hydride (0.27 g, 7.2 mmol) as a slurry in tetrahydrofuran (5 mL). The mixture was heated to reflux for 100 minutes, then cooled in an ice-water bath and quenched with water (0.6 mL), 15% aqueous KOH (0.6 mL), and also crushed sodium sulfate decahydrate (14 g). The mixture was stirred mixture at room temperature for 30 minutes, then filtered and washed with ethyl acetate. The organic layer was concentrated to a yellow oil that was purified by flash chromatography (ammonium hydroxide/methanol/dichloromethane) to afford pure 5-(1H-indol-5-yl)-2,3,4,5-tetrahydro-1H-benzo[c]azepine as a colorless foam (0.20 g, MS (M+H)=263), as well as some product (0.23 g) contaminated with an uncharacterized tetrahydrofuran-aluminum complex as a colorless foam. The contaminated product was dissolved in 1:1 ethyl acetate:diethyl ether (5 mL), and 1.0 M HCl in diethyl ether (0.9 mL) was added dropwise, under a blanket of dry nitrogen gas. The white solid precipitate was collected by filtration and washed with ice-cold diethyl ether and tetrahydrofuran. The solid was suspended in ethanol and evaporated to dryness under reduced pressure, and that process was repeated to afford pure 5-(1H-indol-5-yl)-2,3,4,5-tetrahydro-1H-benzo[c]azepine hydrochloride as an off-white powder (0.16 g).

Workup

  1. temperatureTo an ice-water bath cooled
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 100 minutes
  4. temperaturecooled in an ice-water bath
  5. customquenched with water (0.6 mL), 15% aqueous KOH (0.6 mL), and also crushed sodium sulfate decahydrate (14 g)
  6. filtrationfiltered
  7. washwashed with ethyl acetate
  8. concentrationThe organic layer was concentrated to a yellow oil that
  9. customwas purified by flash chromatography (ammonium hydroxide/methanol/dichloromethane)

Sources & evidence

ORD record
ord-2e398ea8112a4ea3958a4d123f3ce66f
Source dataset
uspto-grants-2009_11
Patent number
US07622462B2

Reaction notes

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