DIETHYL 1H-PYRROLO[2,3-B]PYRIDINE-2,6-DICARBOXYLATE synthesis

Yield:1311569-08-0 84%

Reaction Conditions:

(diphenylphosphin)ferrocene;palladium diacetate in ethanol at 110; under 12929 Torr; for 15 h;Autoclave;Inert atmosphere;

Steps:

D.6

Step 6: Synthesis of diethyl lH-pyrrolo[2,3-b]pyridine-2,6-dicarboxylateReagents are charged into a 600 mL autoclave in the following order: ethanol (350 mL), sodium acetate (17.0 g, 200 mmol), 6-chloro-lH-pyrrolo[2,3-b]pyridine-2-carboxylic acid ethyl ester (24 g, 107 mmol), l,l'-bis-(diphenylphosphino)ferrocene (2.5 g, 2.25 mmol [2.25 mol%]), and palladium acetate (180 mg, 0.75 mmol [0.75 mol %]). The air in the autoclave is replaced with carbon monoxide and the pressure is adjusted to 250 psi. The reaction is then heated to 110 °C for 15 h. The reaction mixture is cooled to room temperature and is filtered through Celite. The solvent is replaced with 500 mL EtOAc followed by 100 mL aqueous wash. The organic layer is concentrated to 50 mL EtOAc and is then heated to 60 °C. After cooling to room temperature, the solids are filtered to afford 20 g of the title compound. The mother liquor is concentrated and is purified by flash column chromatography using gradient elution of 20-60% ethyl acetate in hexanes to afford an additional 3.5 g of title compound which affords total of 23.5 g in 84% isolated yield.

References:

WO2011/71725,2011,A1 Location in patent:Page/Page column 51