Methyl 3-bromo-5-(iodomethyl)-4-methylbenzoate → Methyl 3-bromo-5-(3-fluorobenzyl)-4-methylbenzoate

Participants

Reaction Conditions

Reaction Steps

To a THF (0.1 M) suspension of CuCN (2 eq.) was added at −78° C. 3-fluorophenyl magnesium bromide (0.5 M solution in THF, 4 eq.) over a period of 5 min. The resulting mixture was stirred at −78° C. for 20 min and then at 0° C. for another 20 min. The now yellow suspension was re-cooled to −78° C. before methyl 3-bromo-5-(iodomethyl)-4-methylbenzoate (1 eq.) from the previous step was added. The resulting mixture was stirred at −78° C. for 20 min, 0° C. for another 20 min and finally at RT for 16 h. The crude reaction mixture was quenched with a 3:1 (v/v) mixture of sat. aq. NH4Cl:conc. NH4OH and then extracted with ether. The combined organic extracts were washed further with water and brine, dried over Na2SO4, filtered and the filtrate concentrated in vacuo. Further purification of the crude product by way of flash chromatography (SiO2, Hex→1:1 (v/v) Hex:EtOAc) afforded the title compound as a colorless oil.

Provenance & Evidence