Ethyl bromodifluoroacetate → Ethyl alpha,alpha-difluoro-2-pyrimidineacetate

Participants

Reaction Steps

A mixture of copper bronze (Aldrich) (5.88 g, 92.5 mmol), DMSO (10 mL), and bromo-difluoro-acetic acid ethyl ester (Advanced Synthesis Technologies) (6.46 mL, 50.4 mmol) was evacuated and flushed with argon three times, and was then stirred at rt for 1 h. Upon standing, the supernatant was dark green. Solid 2-iodopyrimidine (8.76 g, 42.5 mmol) (J. Org. Chem. 67:6550, 2002) was then added, the flask was again evacuated and flushed with argon three times, and stirred at rt for 14 h (mild initial warming of flask spontaneously occurred). The resulting immobile dark brown paste was diluted with saturated NH4Cl (175 mL) and EtOAc (150 mL), the mixture was filtered through a pad of Celite, and the filter cake washed with EtOAc (2×50 mL). The blue aqueous layer filtrate was extracted with EtOAc (1×50 mL), and the combined filtrate clear yellow organic layers were washed with saturated NH4Cl (2×100 mL), 10% w/v EDTA trisodium (1×100 mL; saturated NaBr needed to break phases), saturated NaCl (1×50 mL), saturated NaBr (1×20 mL), dried (2×Na2SO4), and concentrated under reduced pressure. Silica flash chromatography of the greenish residue (1:1 hexanes/EtOAc eluent) provided the title compound as a nearly colorless oil with a greenish precipitate (1.75 g, 20%).

Provenance & Evidence