Ethyl bromoacetate → Diethyl 3-cyano-3-(6-methoxypyridin-3-yl)pentanedioate

Participants

Reaction Conditions

Reaction Steps

10.12 ml (20.25 mmol) of lithium diisopropylamide are introduced in 22 ml of anhydrous tetrahydrofuran in a 100 ml three-necked round-bottomed flask under an argon atmosphere at −78° C. 1.00 g (6.75 mmol) of (6-methoxypyridin-3-yl)acetonitrile (WO2004/111031) in solution of 5 ml of anhydrous tetrahydrofuran is added. The reaction mixture is subsequently brought back gently to 0° C. and stirred at this temperature for one hour. The reaction medium is then cooled to −78° C. and 2.25 ml (20.25 mmol) of ethyl bromoacetate are added dropwise. The resulting mixture is subsequently brought back slowly to ambient temperature and then left stirring for 12 hours. The reaction medium is subsequently poured into a saturated aqueous ammonium chloride solution and extracted twice with diethyl ether. The organic phases are combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue obtained is purified by chromatography on a column of silica gel, elution being carried out with a mixture of cyclohexane and ethyl acetate in the proportions of 90/10.

Provenance & Evidence