Methyl acetoacetate → Methyl 2-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylate

HRID 1526984Notes

Reaction equation

HRID 1526984 reaction equation
I[C:2]1[C:3]([NH2:8])=[N:4][CH:5]=[CH:6][CH:7]=1.[C:9]([O:15][CH3:16])(=[O:14])[CH2:10][C:11]([CH3:13])=O.C1(C2C(O)=CC=C3C=2C=CC=C3)C(O)=CC=C2C=1C=CC=C2.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.[Cu](I)I.C(OCC)(=O)C>[CH3:13][C:11]1[NH:8][C:3]2=[N:4][CH:5]=[CH:6][CH:7]=[C:2]2[C:10]=1[C:9]([O:15][CH3:16])=[O:14]

Participants

8

Reactant 4

HCID 7757Methyl acetoacetateHCID 10796Cesium carbonateHCID 11762BinolHCID 27631512-Amino-3-iodopyridine

Product 1

HCID 89740922Methyl 2-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylateYield 21.5%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-iodopyridin-2-amine (5.5 g, 25 mmol) in dimethylsulfoxide (40 mL) were added methyl acetoacetate (3.48 g, 30 mmol), copper iodide (476 mg, 2.5 mmol), 1,1′-binaphthyl-2,2′-diol (1.43 g, 5.0 mmol) and cesium carbonate (8.15 g, 25 mmol). The resultant mixture was stirred at 50° C. for 4 hours. To the reaction mixture was added ethyl acetate (400 mL). The organic phase was washed with brine (80 mL×3), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give crude product which was purified by column chromatography (petroleum ether/ethyl acetate=4:1) to afford methyl 2-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylate (1.02 g, 21.4%) as a white solid. 1H NMR (300 MHz, CD3OD): δ 8.46-8.43 (m, 1H), 7.61-6.69 (m, 2H), 3.89 (s, 3H), 2.73 (s, 3H).

Workup

  1. washThe organic phase was washed with brine (80 mL×3)
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give crude product which
  6. customwas purified by column chromatography (petroleum ether/ethyl acetate=4:1)

Sources & evidence

ORD record
ord-8d60c707503643559411590d1435e250
Source dataset
uspto-grants-2015_07
Patent number
US09085583B2

Reaction notes

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