Chloroiodomethane → tert-Butyl 1-[(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}-phenyl)(cyclopropyloxy)methyl]cyclopropanecarboxylate

Participants

Reaction Steps

68 mg (0.52 mmol) of zinc/copper pair were taken up in 5 ml of abs. diethyl ether, and 41 μl (0.56 mmol) of chloroiodomethane were added at room temperature. A solution of 200 mg (0.35 mmol) of tert-butyl 1-[(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]-amino}phenyl)(vinyloxy)methyl]cyclopropanecarboxylate (as diastereomer mixture) in 10 ml of abs. diethyl ether was then added dropwise to the reaction mixture. The reaction solution was then heated to reflux and stirred overnight. After cooling, the solution was filtered through kieselguhr and the kieselguhr was washed repeatedly with diethyl ether. The filtrate obtained was washed with saturated aqueous sodium bicarbonate solution and with water, dried over magnesium sulphate and concentrated to dryness under reduced pressure. The residue was purified by preparative RP-HPLC (mobile phase methanol/water 80:20, isocratic). This gave 54 mg (27% of theory) of the target compound.

Provenance & Evidence