Diethyl Malonate → Ethyl {3,4-difluoro-5-[(phenylmethyl)oxy]phenyl}acetate

Participants

Reaction Conditions

Reaction Steps

5-bromo-1,2-difluoro-3-[(phenylmethyl)oxy]benzene (10 g, 33.3 mmol), diethyl propanedioate (6.9 g, 43.3 mmol), Cs2CO3 (108 g, 333 mmol), and dioxane (200 mL) were combined in a sealed flask and N2 was bubbled through the solution for 15 minutes. Pd(t-Bu3P)2 (1.7 g, 3.33 mmol) was then added and the flask was sealed. The solution was heated to 80° C. and stirred vigorously. After 8 h, the temperature was increased to 120° C. After 3 days, it was cooled and H2O and EtOAc were added. The aqueous layer washed with EtOAc (3×). The combined organic extracts were concentrated, and purified by Biotage (in two batches) to afford 1.82 g of the title compound (21%).

Provenance & Evidence