Acetic Acid → HCID 86659881, compound

HRID 2360160Notes

Reaction equation

HRID 2360160 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[CH:6]2.[C:12](O)(=O)[CH3:13].[C:16]([BH3-])#[N:17].[Na+].[C:20]([O-])(O)=O.[Na+].C(O[CH2:29][CH3:30])(=O)C>O1CCCC1>[N:17]1[CH:16]=[CH:30][CH:29]=[CH:20][C:12]=1[CH2:13][N:8]1[C:9]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:11][CH:10]=2)[CH2:6][CH2:7]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 8857Ethyl AcetateHCID 138725-MethoxyindoleHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 86659881HCID 86659881, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-methoxyindole (758 mg, 5.15 mmol) in a 1:1 solution (7.7 mL) of acetic acid and tetrahydrofuran was added sodium cyanoborohydride (1.13 g, 18.0 mmol) at room temperature. After being stirred for 1 h, 2-pyridinecarboxyaldehyde (0.98 mL, 10.3 mmol) was added with additional stirring for 1 h. After the reaction mixture was neutralized by saturated NaHCO3 aqueous solution, the reaction mixture was diluted with ethyl acetate. The separated organic layer was washed with brine, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified with silica gel column chromatography (hexane/ethyl acetate=80/20 to 40/60) to obtain 1-(2-pyridylmethyl)-5-methoxyindoline (543 mg, 44%). To the above product was added a solution of 50% hydrogen bromide-acetic acid solution (10 mL) at room temperature. After the reaction mixture was stirred at 105° C. for 30 min, the reaction mixture was neutralized by saturated NaHCO3 aqueous solution, and the solution was extracted with ethyl acetate. The extract was washed with brine, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20 to 70/30) to obtain the title compound (313 mg, 61%) as a sticky oil.

Workup

  1. addition2-pyridinecarboxyaldehyde (0.98 mL, 10.3 mmol) was added
  2. stirringwith additional stirring for 1 h
  3. washThe separated organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationAfter filtration
  6. concentrationthe filtrate was concentrated in vacuo
  7. customthe residue was purified with silica gel column chromatography (hexane/ethyl acetate=80/20 to 40/60)

Sources & evidence

ORD record
ord-3067fce3dbe34476adff0e6762cab3cc
Source dataset
uspto-grants-2014_04
Patent number
US08686024B2

Reaction notes

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