Lithium diisopropylamide → 7-Bromo-3-chloro-5H-chromeno[2,3-c]pyridin-5-one

Participants

Reaction Conditions

Reaction Steps

A solution of 5-bromo-2-(6-chloropyridin-3-yloxy)-N,N-diethylbenzamide (457.5 g, 1.23 mol) in THF (3 L) was cooled to −74 to −78° C. and treated with a solution of LDA (2M in heptane/THF/ethyl benzene, 2.25 L, 4.5 mol. After the addition was complete, the solution was stirred for 30 min at −78° C. The cold bath was removed and then the reaction was quenched with saturated aqueous NH4Cl (1 L), maintaining the temperature below 10° C. The mixture was added to an addition funnel and the layers were separated. The aqueous layer was extracted with EtOAc (3×2.5 L). The combined organic layers were dried over sodium sulfate, filtered and passed through a pad of silica gel. The filtrate was evaporated, and the residue was triturated with DCM to give 35 g of 7-bromo-3-chloro-5H-chromeno[2,3-c]pyridin-5-one. The mother liquor was evaporated and the solid thus obtained was purified by recrystallization using dichloromethane/hexanes to give 90 g of 7-bromo-3-chloro-5H-chromeno[2,3-c]pyridin-5-one.

Provenance & Evidence