Chlorotrimethylsilane → Ethyl (3S)-2-bromo-4,4,4-trifluoro-3-methylbutanoate

Participants

Reaction Conditions

Reaction Steps

91.2 ml (228 mmol) of a 2.5 M solution of n-butyllithium solution in hexane were added to a solution, cooled to −40° C., of 32.0 ml (228 mmol) of diisopropylamine in 160 ml of abs. THF. The resulting LDA solution was stirred at −40° C. for 30 min and then cooled to −78° C., and 52.4 ml (413 mmol) of chlorotrimethylsilane were subsequently added dropwise. After 5 min, 40.0 g (217.2 mmol) of (+)-ethyl (3R)-4,4,4-trifluoro-3-methylbutanoate, dissolved in 40 ml of abs. THF, were added dropwise over a period of 1 h. At −78° C., in three portions a total of 40.59 g (228 mmol) of N-bromosuccinimide were added to the resulting suspension, and the mixture was then slowly warmed to RT overnight. Water was added carefully, and the reaction mixture was extracted with ethyl acetate. The organic phase was washed successively with 1 N hydrochloric acid, sat. sodium bicarbonate solution and sat. sodium chloride solution, dried over sodium sulphate and concentrated under reduced pressure without heating. 130 ml of diethyl ether were added to the resulting suspension, and the mixture was kept at 4° C. overnight. The undissolved solid formed was then filtered off and discarded. The filtrate was concentrated under reduced pressure without heating and the residue was briefly dried under high vacuum. This gave 48.5 g of ethyl (3S)-2-bromo-4,4,4-trifluoro-3-methylbutanoate (diastereomer mixture) as a crude product.

Provenance & Evidence