Cyclohexane → Ethyl 3-(4-bromo-2-fluorophenyl)prop-2-ynoate

Participants

Reaction Conditions

Reaction Steps

In a 100 mL round-bottomed flask, 4-bromo-1-ethynyl-2-fluorobenzene (2.0 g, 10.0 mmol) was combined with THF (28 ml) to give a brown solution. The solution was cooled to −78° C. and 1.5M LDA in cyclohexane (16.4 mL, 24.6 mmol, Eq: 2.45) was added via syringe. The reaction was stirred at −78° C. for 20 mins, ethyl chloroformate (5.42 g, 4.8 mL, 50.0 mmol, Eq: 4.97) was added at −78° C. and the reaction was stirred at room temp for 2 h under argon. The reaction was quenched with saturated NH4Cl and diluted with EtOAc. The aqueous layer was back-extracted with EtOAc. The organic layers were combined, washed with 1 M HCl (2×50 mL), H2O (1×50 mL), saturated NaHCO3 (1×50 mL) and brine (1×25 mL), dried over Na2SO4 and concentrated in vacuo to a dark red oil. The crude material was purified by flash chromatography (silica gel, 220 g, 0% to 20% EtOAc in heptane) to afford a pure fraction (4.49 g, 46%) of the desired product as an off white solid. The less pure fraction was stripped and the residue was recrystallized from EtOAc/hexane to afford an additional 1.64 g (17%) of the desired product as a pink powder. 1H NMR (CDCl3) δ ppm 7.40-7.53 (m, 1H), 7.28-7.39 (m, 2H), 4.28 (q, J=7.0 Hz, 2H), 1.32 (t, J=7.0 Hz, 3H).

Provenance & Evidence