Aluminium lithium hydride → methoxy-3-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 228256Notes

Reaction equation

HRID 228256 reaction equation
[CH3:1][O:2][CH:3]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[CH2:7][CH2:6][N:5]([CH3:14])[C:4]1=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1.CCOCC.C1COCC1>[CH3:1][O:2][CH:3]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[CH2:7][CH2:6][N:5]([CH3:14])[CH2:4]1

Participants

5

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 68749213Methoxy-3-methyl-1,3,4,5-tetrahydrobenzo[d]azepin-2-one

Product 1

HCID 68748342methoxy-3-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 1,028.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21868444Ether tetrahydrofuranSolvent

Procedure

Dissolve methoxy-3-methyl-1,3,4,5-tetrahydrobenzo[d]azepin-2-one (375 g, 183 mmol, 1.0 eq) in THF (2.5 L) and add the solution via an addition funnel over 1 hour to slurry of lithium aluminium hydride (LAH) (175 g, 457 mmol, 2.5 eq) in ether/THF (4.5 L/2 L) in a 22 L reaction vessel under nitrogen while cooled in an ice/acetone bath. Add the starting amide at a rate to maintain the reaction temperature below 30° C. Stir the resulting mixture for 3 hours at room temperature under nitrogen. The reaction is determined to be complete by TLC. Cool the reaction mixture in an ice/acetone bath and quench slowly over 2 hours (off-gassing, exothermic) with water (175 mL) and 5.0 N NaOH solution (350 mL) added in succession. Filter the slurry and wash the solids with THF. Add sodium sulfate to the filtrate to remove any excess water, and then filter. Concentrate the filtrate down under vacuum to a dark oil to obtain the product methoxy-3-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (360 g, quantitative yield).

Workup

  1. additionadd the solution via an addition funnel over 1 hour
  2. temperaturewhile cooled in an ice/acetone bath
  3. temperatureto maintain the reaction temperature below 30° C
  4. temperatureCool the reaction mixture in an ice/acetone bath
  5. customquench slowly over 2 hours (off-gassing, exothermic) with water (175 mL) and 5.0 N NaOH solution (350 mL)
  6. additionadded in succession
  7. filtrationFilter the slurry
  8. washwash the solids with THF
  9. customAdd sodium sulfate to the filtrate to remove any excess water
  10. filtrationfilter
  11. concentrationConcentrate the filtrate down under vacuum to a dark oil

Sources & evidence

ORD record
ord-01d29f776a444f8ca05f789c9d7b853c
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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