Phosphorus oxychloride → tert-butyl 2-(2,6-difluorophenylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

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Reaction Steps

To a suspension of lithium 1-(tert-butoxycarbonyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (589 mg, 2.18 mmol, Eq: 1.00) and 2,6-difluoroaniline (480 mg, 0.4 mL, 3.72 mmol, Eq: 1.71) in pyridine (7 mL) (ice-bath) was added dropwise phosphoryl trichloride (660 mg, 0.4 mL, 4.3 mmol, Eq: 1.97). The cooling bath was removed and the resulting yellow/orange suspension was stirred at rt for 2 h. The reaction mixture was concentrated in vacuo and the residue was treated with water (20 mL). The resulting mixture was extracted with EtOAc (2×20 mL) and the combined organic layers were washed with brine (1×5 mL). The crude material was purified by flash chromatography (silica gel, 24 g, 0% to 100% EtOAc in DCM/hexanes (1:1)). After the combined fractions were concentrated, the off-white solid was treated with 5% MeOH/ether (˜10 mL) to give tert-butyl 2-(2,6-difluorophenylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate as a white solid (532 mg).

Provenance & Evidence