Acetaldehyde → 4-Ethyl-1,3,4,5-tetrahydropyrrolo[4,3,2-de] isoquinoline

HRID 1096485Notes

Reaction equation

HRID 1096485 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[NH:7]1[C:17]2[C:18]3[C:9]([CH2:10][NH:11][C:12](=O)[C:13]=3[CH:14]=[CH:15][CH:16]=2)=[CH:8]1.N1C2C3[C:22](CNCC=3C=CC=2)=[CH:21]1.C(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.CO>[CH2:21]([N:11]1[CH2:10][C:9]2=[CH:8][NH:7][C:17]3[C:18]2=[C:13]([CH:14]=[CH:15][CH:16]=3)[CH2:12]1)[CH3:22]

Participants

8

Reactant 5

HCID 177AcetaldehydeHCID 3041095Pyrrolo(4,3,2-de)isoquinolin-5(1H)-one, 3,4-dihydro-HCID 3041097HCID 3041097, compoundHCID 5049666Sodium triacetoxyborohydrideHCID 21226445Aluminium lithium hydride

Product 1

HCID 30411034-Ethyl-1,3,4,5-tetrahydropyrrolo[4,3,2-de] isoquinoline

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

LiAlH4 (0.440 g, 11.6 mmol) was added in portions to a solution of 3,4-dihydropyrrolo[4,3,2-de]isoquinolin-5(1H)-one, Intermediate 1 (0.4 g, 2.32 mmol) in dry THF (20 ml). The mixture was brought to reflux for 3 hours, cooled, diluted with aqueous THF and filtered. The solid cake was washed with THF (2×) and the residue was evaporated to give a light brown solid. This brown solid was dissolved in MeOH (20 ml) and acetaldehyde (0.334 g, 7.6 mmol) and sodium triacetoxy borohydride (0.482 g, 2.3 mmol) were added. The mixture was stirred for 1 hour and evaporated to half its volume and partitioned between 1N Na2CO3 and dichloromethane. The organic phase was washed with brine, dried (MgSO4) and evaporated. The crude product was purified by flash chromatography using 10% MeOH to 50% MeOH in dichloromethane with 1% NEt3. Yield: 142 mg. Grey solid. MS m/z 187 [M+H]+.

Workup

  1. temperatureto reflux for 3 hours
  2. temperaturecooled
  3. filtrationfiltered
  4. washThe solid cake was washed with THF (2×)
  5. customthe residue was evaporated
  6. customto give a light brown solid
  7. customevaporated to half its volume
  8. custompartitioned between 1N Na2CO3 and dichloromethane
  9. washThe organic phase was washed with brine
  10. dry with materialdried (MgSO4)
  11. customevaporated
  12. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-9e29b67e4cd441d5870870b2c32d782a
Source dataset
uspto-grants-2012_03
Patent number
US08138333B2

Reaction notes

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