Dimethylformamide → HCID 14539461, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of NaH (10.47 g, 60% by wt, 0.2616 mol) in THF (1.40 L), at 13.1° C. under argon, was added a solution of 4-bromo-3-hydroxybenzoic acid (28.11 g, 0.130 mol) in THF (400 ml) over 1.25 h maintaining the internal temperature in the range 4-15° C. After 1.5 h a solution of benzyl bromide (44.3 g, 0.2591 mol) in THF (70 ml) was added over 0.5 h. To the resulting suspension was added DMF (500 ml) and the mixture allowed to warm to room temperature. After a further 15 h extra DMF was added (1.5 L) to the suspension. After approximately 30 minutes the reaction mixture was essentially clear and TLC analysis (25% EtOAc/hexane) indicated that effectively all of the starting material had been consumed. The reaction mixture was quenched with dilute ammonium chloride (100 ml) and concentrated in vacuo. To the concentrate was added ethyl acetate (1.0 L) and dilute ammonium chloride (1.0 L) and the fractions separated. The aqueous fraction was back extracted with ethyl acetate (1×450 ml and 1×300 ml). The total organic fraction was dried over sodium sulphate, filtered and concentrated in vacuo. The resulting solid was crystallised from ethanol:water (9:1; vol:vol, 200 ml), heated at reflux, to which was added ethanol (65 ml) until all the material had dissolved. Water was then added dropwise (17 ml), followed by extra ethanol (8.0 ml). The resulting solution was allowed to slowly cool to ambient temperature. The resulting solid was filtered off and dried (44.54 g). This solid was then dissolved in hot ethanol (227 ml) and water (5.0 ml) added and then allowed to slowly cool to ambient temperature. The resulting crystals were filtered off, washed with cold ethanol (25 ml) and dried in a vacuum oven at 50° C. to give the title compound (36.79 g, yield 71.5%). mp=80.5-81.5° C.

Provenance & Evidence