1-Chloro-4-iodobenzene → HCID 70914950, compound

Participants

Reaction Conditions

Reaction Steps

Under argon, 6.2 g (26 mmol) of 1-chloro-4-iodobenzene were dissolved in 50 ml of THF and cooled to −78° C. 24 ml (31.2 mmol) of a 1.3 M solution of isopropylmagnesium chloride×lithium chloride in THF were then slowly added dropwise. The reaction solution was then slowly warmed to −40° C. and stirred at this temperature for 2 h. The reaction solution was then warmed to −10° C., and 495 mg (2.6 mmol) of copper(I) iodide were added. 5 g (24.97 mmol) of dimethyl (3-methylbutan-2-ylidene)malonate, dissolved in 30 ml of THF, were then slowly added dropwise to the reaction solution. The resulting reaction mixture was slowly warmed to room temperature and stirred at this temperature for 1 h. The mixture was then cooled to 0° C., and ice-cold 1 M hydrochloric acid (pH˜2) was added carefully. The phases were separated, the aqueous phase was then extracted three more times with ethyl acetate and the combined organic phases were dried over magnesium sulphate, filtered and concentrated to dryness. The resulting crude product was initially pre-purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 20:1). The product was then re-purified by preparative RP-HPLC (mobile phase methanol/water). This gave 3.38 g (42% of theory) of the target compound.

Provenance & Evidence