Bromine → Methyl 4-bromo-3-methylbutanoate

Participants

Reaction Conditions

Reaction Steps

Methyl 3-methylglutarate(37 g; 231 mmol) was added to 1M NaOH (231 mL; 231 mmol) causing the solution to warm slightly. This solution was added to a solution of silver nitrate (39.2 g; 231 mmol) in water (184 mL) at 60° C. A fine white precipitate formed immediately. The mixture was cooled and stirred in an ice bath for 1 h before being filtered, washed with water, acetone and ether and partially dried on the filter. The solid was then dried over night at 80° C. in a vacuum oven to give the silver salt of the methyl 3-methylglutarate(49 g, 79%) as a pale brown solid. The silver salt of the methyl 3-methylglutarate (49 g; 184 mmol) was suspended in carbon tetrachloride (245 mL) and bromine (9.5 mL) slowly added. The reaction mixture warmed to ≈30° C. during this process and effervescence was seen. The reaction mixture was maintained at this temperature by the rate of addition of bromine. After the final addition of bromine the viscous mixture was stirred for 0.5 h before being heated at reflux for 1 h. After cooling, the pale yellow precipitate was removed by filtration and the filtrate washed with 1M aqueous sodium thiosulphate, brine, dried (phase separation paper) and concentrated under reduced pressure. This gave a pale yellow oil which contained 15% of methyl 3-methylglutarate as an impurity by 1H NMR. This was removed by taking the oil up in dichloromethane (DCM) and washing with 1M NaOH. Drying and concentration as above gave (±) methyl 4-bromo-3-methylbutyrate (25 g, 70%) as a pale yellow oil.

Provenance & Evidence