1-Bromo-4-fluorobenzene → {3-Cyano-6-[(4-fluorophenyl)carbonyl]phenyl}methyl 2,2-dimethylpropanoate

Participants

Reaction Steps

A solution of 4-fluorophenylmagnesium bromide, prepared from 4-fluorobromobenzene (19.2 g, 0.11 mol) and magnesium turnings (3.2 g, 0.13 mol) in dry THF (100 mL), was added dropwise to a suspension of 5-cyanophthalid (15.9 g, 0.1 mol) in dry THF (150 mL). The temperature was kept below 5° C. After the addition was complete, the reaction mixture was stirred overnight at room temperature. Pivaloylchloride (13.3 g, 0.11 mol) was added to the reaction mixture and the temperature was raised to 60° C. for 2 hours. The resulting solution was added to a saturated solution of NH4Cl (100 mL, aq) and ice (50 g). Diethylether (100 mL) was added and the phases were separated. The organic phase was washed with 0.1 N NaOH (2×100 mL) and water (100 mL) and the organic phase was dried with MgSO4 (20 g). Evaporation of the solvents gave a crude title compound (29.8 g, 88%) as an oil which was deemed sufficiently pure for further reaction. A pure sample is obtained by crystallisation from EtOAc/n-Heptane (1:9). The title compound is obtained as off white crystals.

Provenance & Evidence