1,4-Dibromobenzene → Methyl 3-(4-bromophenyl)-3-hydroxycyclobutane-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

Into a 20-L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed tetrahydrofuran (12 L), 1,4-dibromobenzene (2020 g, 8.56 mol, 1.03 equiv), followed by the addition of n-BuLi (3566 mL, 1.03 equiv, 2.4 M) dropwise with stirring at −78° C. The mixture was stirred at −78° C. for 1 h. Into another 20-L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of methyl 3-oxocyclobutane-1-carboxylate (1064 g, 8.30 mol, 1.00 equiv) in tetrahydrofuran (4 L). To this was added the resulting solution in the first flask dropwise with stirring at −78° C. The resulting solution was stirred overnight at 25° C. This reaction was repeated for 2 more times. The reaction was then quenched by the addition of 15 L of saturated aqueous NH4Cl, concentrated under vacuum, diluted with 15 L of H2O and extracted with 2×5 L of ethyl acetate. The organic layers were combined, washed with 1×8 L of brine, dried over anhydrous sodium sulfate and concentrated under vacuum to afford 6500 g (92%) of methyl 3-(4-bromophenyl)-3-hydroxycyclobutane-1-carboxylate as a dark red oil.

Provenance & Evidence