Benzaldehyde → HCID 57750059, compound

HRID 340404Notes

Reaction equation

HRID 340404 reaction equation
[CH2:1]1[C:13]2[C:12]3[CH:11]=[C:10]([C:14]([O:16][CH3:17])=[O:15])[CH:9]=[CH:8][C:7]=3[NH:6][C:5]=2[CH2:4][CH2:3][N:2]1[C:18](OC(C)(C)C)=O.C(=O)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(O)(C(F)(F)F)=O>[CH2:18]([N:2]1[CH2:3][CH2:4][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([C:14]([O:16][CH3:17])=[O:15])=[CH:11][C:12]=3[C:13]=2[CH2:1]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 240BenzaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 57750067HCID 57750067, compound

Product 1

HCID 57750059HCID 57750059, compoundYield 66.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 2-tert-butyl 8-methyl 3,4-dihydro-1H-pyrido[4,3-b]indole-2,8(5H)-dicarboxylate (0.50 g, 1.5 mmol) in DCM (5.0 mL), TFA (5.0 mL) was added. After allowing the reaction mixture to stir at room temperature for 1 h, the volatiles were evaporated, DCM and toluene (20 mL) were added and the volatiles evaporated (2×). The resulting residue was dissolved in THF/MeOH (4:1, 10 mL) and benzaldehyde (0.17 mL, 0.18 g, 1.7 mmol) and sodium triacetoxyborohydride (0.485 g, 2.3 mmol) were added. The reaction mixture was allowed to stir at room temperature overnight and 4 more equivalents of the aldehyde and reducing agent were added to cause the reaction to go to completion. The reaction mixture was then poured into saturated sodium bicarbonate solution (300 mL). The layers were separated, and the aqueous layer was extracted with DCM (3×100 mL). The combined organic layers were washed with brine (2×50 mL), dried (MgSO4), filtered and concentrated to give a foamy residue. Column chromatography (DCM→3% MeOH/DCM) provided methyl 2-benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxylate (12a in Scheme 1(h)) as a white solid (0.32 g, 66%). 1H NMR (CD3OD, 300 MHz) 8.17 (d, J=1.1 Hz, 1H), 7.73 (dd, J=8.7, 1.8 Hz, 1H), 7.44-7.27 (m, 6H), 3.88 (s, 3H), 3.83 (s, 2H), 3.73 (s, 2H), 2.95-2.88 (m, 4H) ppm; MS (ES) 321 (M+H).

Workup

  1. customthe volatiles were evaporated
  2. additionDCM and toluene (20 mL) were added
  3. customthe volatiles evaporated (2×)
  4. dissolutionThe resulting residue was dissolved in THF/MeOH (4:1, 10 mL)
  5. stirringto stir at room temperature overnight
  6. additionwere added
  7. customthe reaction
  8. customThe layers were separated
  9. extractionthe aqueous layer was extracted with DCM (3×100 mL)
  10. washThe combined organic layers were washed with brine (2×50 mL)
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customto give a foamy residue

Sources & evidence

ORD record
ord-f09c27feab434446ab5bf4d6be31a462
Source dataset
uspto-grants-2014_11
Patent number
US08895578B2

Reaction notes

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