Compound 3

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Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

A flame-dried nitrogen-flushed 500 mL three-necked flask was charged with 1,1-dibromo-2-(chloromethyl)cyclopropane 2 (3.85 g, 15.51 mmol, 1.2 equiv) and Et₂O (80 mL). The solution was cooled to –78 °C (dry ice/acetone) then methyl lithium (in Et₂O, 15.51 mmol, 1.2 equiv)^A was added at a rate of 0.6 mL/min (syringe pump). The reaction was stirred for 30 min at –78°C followed by 1 h at –50 °C^B. The solution was then cooled back to –78 °C (dry ice/acetone) and a high vacuum was applied for 2 min to remove the volatile MeBr. tert-Butyl lithium (in pentane, 15.51 mmol, 1.2 equiv)^C was then added at a rate of 0.6 mL/min (syringe pump) and stirred for 20 min. The product was used directly in the next step. Notes: (A) Methyl lithium should be carefully titrated before use. (B) A ‒50 °C cooling bath is most conveniently prepared by adding chunks of dry ice to an acetone bath until the desired temperature is reached. The reaction is carefully, but quickly, transferred from the ‒78 °C bath into the ‒50 °C bath. (C) tert-Butyl lithium should be carefully titrated prior to use.