Benzo[b]thiophene-3-acetonitrile → Benzo[b]thiophene-3-ethanamine

HRID 1179058Notes

Reaction equation

HRID 1179058 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl-].[Al+3].[Cl-].[Cl-].[S:11]1[CH:15]=[C:14]([CH2:16][C:17]#[N:18])[C:13]2[CH:19]=[CH:20][CH:21]=[CH:22][C:12]1=2.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>C(OCC)C>[S:11]1[CH:15]=[C:14]([CH2:16][CH2:17][NH2:18])[C:13]2[CH:19]=[CH:20][CH:21]=[CH:22][C:12]1=2

Participants

6

Reactant 4

HCID 76681Benzo[b]thiophene-3-acetonitrileHCID 6451240Aluminum(III) Chloride2×HCID 9855836Potassium sodium tartarateHCID 21226445Aluminium lithium hydride2×

Product 1

HCID 26743Benzo[b]thiophene-3-ethanamineYield 68.9%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

Lithium aluminium hydride (1.16 g, 30.3 mmol) was suspended in dry diethyl ether (100 ml). Anhydrous aluminium chloride (4.04 g, 30.3 mmol) was introduced into this suspension under argon. After five minutes, a solution of benzo[b]thiophene-3-acetonitrile (5.25 g, 30.3 mmol) in dry diethyl ether (70 ml) was added. When the addition was complete, the mixture was heated under reflux for four days. Lithium aluminium hydride (930 mg) and aluminium chloride (500 mg) were added again to the reaction mixture and the mixture was heated under reflux for a further eight hours. For working up, it was neutralized with an aqueous solution of potassium sodium tartrate (80 ml, 20 wt. %). When the evolution of gas had ended, the phases were separated and the cloudy aqueous phase was filtered off with suction over a glass frit. The residue on the frit was washed with ethyl acetate and the clear aqueous phase was extracted with ethyl acetate (3×50 ml). The organic phases were dried over sodium sulfate and filtered and the filtrate was concentrated. Crude benzo[b]thiophen-3-ylethylamine (3.7 g) was obtained as a red-brown oil. Treatment with methanolic hydrochloric acid gave a tacky hydrochloride, which was immediately converted back into the free base. 794 mg (15%) benzo[b]thiophen-3-yl-ethylamine were obtained as a yellow oil, which was employed for the further synthesis.

Workup

  1. additionWhen the addition
  2. temperaturethe mixture was heated
  3. temperatureunder reflux for four days
  4. temperaturethe mixture was heated
  5. temperatureunder reflux for a further eight hours
  6. customthe phases were separated
  7. filtrationthe cloudy aqueous phase was filtered off with suction over a glass frit
  8. washThe residue on the frit was washed with ethyl acetate
  9. extractionthe clear aqueous phase was extracted with ethyl acetate (3×50 ml)
  10. dry with materialThe organic phases were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-221e93e20e9644e4b29182097045689e
Source dataset
uspto-grants-2007_10
Patent number
US07276518B2

Reaction notes

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