2-Chloro-4-nitrobenzoic acid → 2-(1,3-Dimethoxy-1,3-dioxopropan-2-yl)-4-nitrobenzoic acid

Participants

Reaction Conditions

Reaction Steps

A solution of 2-chloro-4-nitrobenzoic acid (75 g, 372 mmol) in dimethyl malonate (900 mL) was perfused with nitrogen for 15 min. Sodium methoxide (48.3 g, 894 mmol) was added in one portion and the contents exothermed to 48° C. Fifteen minutes later, copper (I) bromide (5.4 g, 37 mmol) was added in one portion and the contents were heated to 70° C. for 24 hrs. The reaction, which was 70% complete as determined by NMR, was subsequently heated to 85° C. for 5 hrs to completely consume the remaining 2-chloro4-nitrobenzoic acid. Water (900 mL) was added to the cooled reaction followed by hexanes (900 mL). The aqueous layer was separated, toluene (900 mL) was added, the mixture was filtered and aqueous layer separated. Fresh toluene (1800 mL) was added to the aqueous layer and the biphasic mixture acidified with 6N aqueous HCl (90 mL). A white precipitate formed and the contents were stirred for 18 hrs. The product was filtered off and dried to give a white solid (78.1 g, 70%) mp 153° C.

Provenance & Evidence