Hydrochloric Acid → Methyl 4-(4-fluorobenzyl)-3-methoxycarbonylbenzoate

Participants

Reaction Steps

A 2.0M solution of 4-fluorobenzyl zinc bromide in tetrahydrofuran (95 ml, 190 mmol; Negishi, E-i. and King, A. O., J.O.C.1977,42,1821) was added dropwise over 20 minutes to a stirred solution of dimethyl 4-bromoisophthalate (20.0 g, 73.2 mmol) and tris(dibenzylideneacetone)dipalladium (0) (0.67 g, 0.73 mmol) in tetrahydrofuran (270 ml) at ambient temperature under an inert atmosphere. During the addition the internal temperature rose to 40° C. The reaction mixture was stirred for 3 hours and then poured into 2M. HCl (1500 ml) cooled in an ice bath and the product extracted into ethyl acetate (3×700 ml). The extracts were washed with water (500 ml), brine (500 ml), dried, and the solvent evaporated under reduced pressure. The residue was taken up in a small quantity of dichloromethane, isohexane added, and the solid, which crystallised from the solution, filtered and dried to give methyl 4-(4-fluorobenzyl)-3-methoxycarbonylbenzoate (10.5 g)

Provenance & Evidence