Hydrochloric Acid → 4-Fluoro-4-methyl-3-oxopentanenitrile

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of 60% NaH/mineral oil (12.48 g, 0.31 mol) in dry THF at 75° C. was added dropwise methyl 2-fluoro-2-methylpropanoate (24 g, 0.2 mol) in dry acetonitrile (16 mL, 0.31 mol) over the course of 45 min. The resulting pale yellow suspension was heated at 70° C. overnight, whereupon analysis by TLC indicated a single new product. After cooling to rt, the mixture was poured into water, acidified to pH˜2 with 2N HCl, and extracted with diethyl ether (1 L). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0-30% EtOAc in petroleum ether to afford 4-fluoro-4-methyl-3-oxopentanenitrile as a colorless oil (18 g, 72% yield). LC-MS (ESI) m/z 128 (M−H)+.

Provenance & Evidence