Methanol → Methyl 7-azaindole-3-glyoxylate

HRID 1036626Notes

Reaction equation

HRID 1036626 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[NH:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][N:12]=2)[CH:7]=[CH:6]1.Cl[C:15](=[O:20])[C:16]([O:18][CH3:19])=[O:17].CO>C(Cl)Cl>[O:20]=[C:15]([C:7]1[C:8]2[C:13](=[N:12][CH:11]=[CH:10][CH:9]=2)[NH:5][CH:6]=1)[C:16]([O:18][CH3:19])=[O:17]

Participants

6

Reactant 4

HCID 887MethanolHCID 92221H-Pyrrolo(2,3-b)pyridineHCID 79846Methyl chloroglyoxylateHCID 6451240Aluminum(III) Chloride

Product 1

HCID 6028556Methyl 7-azaindole-3-glyoxylateYield 74.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of aluminum chloride (56.4 g, 423 mmol, 5 equiv.) in DCM (50 mL) was added 7-azaindole (10.0 g, 85 mmol). After 1 h at room temperature the resulting mixture was cooled to 0° C. and methyl chlorooxoacetate (51.9 g, 423 mmol, 5 equiv.) was added dropwise. After a period of 18 h at room temperature the reaction mixture was cooled to 0° C. and methanol (300 mL) was added. After a period of 0.5 h at room temperature, the solvents were evaporated. DCM (500 mL) and saturated NaHCO3 (600 mL) were added. The organic layer was separated and the water extracted with DCM (250 mL). The organic phases were combined and stirred for 18 h with a solution of potassium sodium tartrate (166 g in 500 mL of water). The organic phase was separated, dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography with 50% ethyl acetate in hexane to provide 13 g of the title compound.

Workup

  1. temperatureAfter a period of 18 h at room temperature the reaction mixture was cooled to 0° C.
  2. customthe solvents were evaporated
  3. additionDCM (500 mL) and saturated NaHCO3 (600 mL) were added
  4. customThe organic layer was separated
  5. extractionthe water extracted with DCM (250 mL)
  6. customThe organic phase was separated
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. customThe residue was purified by flash chromatography with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-fd25d2dc12374f09b7ac71a64a143638
Source dataset
uspto-grants-2013_10
Patent number
US08546422B2

Reaction notes

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