2-Bromothiophene → (2S)-2-{[(S)-(4-bromophenyl)(thien-2-yl)methyl]oxy}-4-methylpentanoic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-bromothiophene (326 mg, 2.0 mmol) in ether (8 mL) was added magnesium turnings (51 mg, 2.1 mmol). The mixture was heated at 50° C. for 1 hour, under a nitrogen atmosphere. The grignard solution was then cooled down to −40° C. and aged until addition. In a second flask, cooled at −40° C., a 0.2M solution of (5S)-2-(4-bromophenyl)-5-isobutyl-1,3-dioxolan-4-one in ether, from step 1 (5.0 mL, 1.0 mmol) was added dropwise to a 1.0M solution of zinc chloride in ether (5.0 mL, 5 mmol). Finally, the grignard solution was added dropwise to the zinc chloride mixture and the reaction was aged for 30 minutes at −40° C. The mixture was allowed to warm to 0° C. and aged for 4 hours. The reaction was then poured into a saturated aqueous solution of NH4Cl and the resulting mixture was extracted 3 times with Et2O. The organic layers were washed with brine, dried and evaporated. The crude product was chromatographed on silica gel using 30% ethyl acetate in hexanes to afford the title compound.

Provenance & Evidence