Benzaldehyde → HCID 68622095, compound

HRID 1244695Notes

Reaction equation

HRID 1244695 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([O:10][C:11]([C:13]1[CH2:30][N:17]2[CH2:18][CH2:19][C:20]3[C:25]([CH:16]2[CH2:15][C:14]=1[NH2:31])=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=3)=[O:12])[CH3:9].[BH4-].[Na+].[CH:34](=O)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C([BH3-])#N.[Na+]>O1CCCC1.C(O)(=O)C>[CH2:8]([O:10][C:11]([CH:13]1[CH2:30][N:17]2[CH2:18][CH2:19][C:20]3[C:25]([CH:16]2[CH2:15][CH:14]1[NH:31][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=3)=[O:12])[CH3:9]

Participants

8

Reactant 5

HCID 240BenzaldehydeHCID 6422Trifluoroacetic acidHCID 4311764Sodium borohydrideHCID 5003444Sodium cyanoborohydrideHCID 59687294Ethyl 2-amino-1,6,7,11b-tetrahydro-9,10-dimethoxy-4H-benzo[a]quinolizine-3-carboxylate

Product 1

HCID 68622095HCID 68622095, compoundYield 51.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

Trifluoroacetic acid (20 mL) was added at 0° C. to a solution of 2-amino-9,10-dimethoxy-1,6,7,11b-tetrahydro-4H-pyrido[2,1-a]isoquinoline-3-carboxylic acid ethyl ester (Example 1a; 2.00 g, 6.02 mmol) in tetrahydrofuran (20 mL), then after 30 min the homogeneous solution was treated with sodium borohydride (474 mg, 12.0 mmol) and stirred for another 40 min. The reaction mixture was concentrated in vacuo and the residue partitioned between 2 M aq. sodium hydroxide solution and dichloromethane. The organic layer was washed with brine, dried (MgSO4) and evaporated. The residue was dissolved in methanol (37 mL) and acetic acid (9 mL) and treated with benzaldehyde (723 mg, 6.81 mmol), then sodium cyanoborohydride (526 mg, 7.95 mmol) was added portionwise at r.t. over 1 h. The reaction mixture was stirred another 15 min, then partitioned between sat. aq. sodium hydrogencarbonate solution and dichoromethane. The organic layer was washed with brine, dried (MgSO4), and evaporated. Chromatrography of the residue (SiO2, CH2Cl2/EtOAc 4:1, after elution of dibenzylated side-product, CH2Cl2/MeOH/NH4OH 95:5:0.25) afforded the title compound (1.31 g, 51%). Red oil, MS (ISP) 425.2 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue partitioned between 2 M aq. sodium hydroxide solution and dichloromethane
  3. washThe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. dissolutionThe residue was dissolved in methanol (37 mL)
  7. stirringThe reaction mixture was stirred another 15 min
  8. custompartitioned between sat. aq. sodium hydrogencarbonate solution and dichoromethane
  9. washThe organic layer was washed with brine
  10. dry with materialdried (MgSO4)
  11. customevaporated
  12. washChromatrography of the residue (SiO2, CH2Cl2/EtOAc 4:1, after elution of dibenzylated side-product, CH2Cl2/MeOH/NH4OH 95:5:0.25)

Sources & evidence

ORD record
ord-e0947b4e91564475934a3e50fe1438c2
Source dataset
uspto-grants-2006_10
Patent number
US07122555B2

Reaction notes

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