Methyl 3-cyclopropyl-2-methyl-3-oxopropanoate → (Z)-methyl 3-cyclopropyl-2-methyl-3-(tosyloxy)acrylate

Participants

Reaction Conditions

Complicated temperature schedule; see notes.procedure_details.

Reaction Steps

To an oven-dried 1000 ml round bottomed flask equipped with a magnetic stir bar under N2 atmosphere was added methyl 3-cyclopropyl-2-methyl-3-oxopropanoate 2 (10.0 g, 64.0 mmol) and THF (100 ml). The mixture was cooled to -78 °C and 1M NaHMDS solution (96.0 ml, 96.0 mmol) was added over 30 min, maintaining the internal temperature below -60 °C, followed by a THF rinse (50 ml). The mixture was aged for 1 h at -78 °C and Ts2O (31.3 g, 96.0 mmol) in THF (200 ml) was added over 1 h, maintaining the internal temperature below -60 °C. The mixture was aged for 20 min at -78 °C, then warmed to 25 °C and aged for 2 h. A thick slurry formed. The reaction was quenched with 300 ml of 0.5M NaHCO3 solution and the phases were separated. The aqueous layer was back-extracted twice with 100 ml of EtOAc. The organic layers were combined and washed with 200 ml of saturated NaCl solution, dried over MgSO4 and filtered. Upon concentration to an oil, the crude product was purified by normal phase column chromatography to give (E)-methyl 3-cyclopropyl-2-methyl-3-(tosyloxy)acrylate 3-(E) in 30% yield and (Z)-methyl 3-cyclopropyl-2-methyl-3-(tosyloxy)acrylate 3-(Z) in 54% yield.

Provenance & Evidence