Triethylamine → 2-[(1R,5S,7R)-3-(10,10-Dimethyl-3,3-dioxo-3lambda6-thia-4-aza-tricyclo[5.2.1.01,5]dec-4-yl)-3-oxo-propenyl]-6-trifluoromethyl-benzoic acid isopropyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of (Z)-3-(2-(isopropoxycarbonyl)-3-(trifluoromethyl)phenyl)acrylic acid (0.90 g, 2.98 mmol) in 30 mL of THF at 0° C. was added triethylamine (0.46 mL, 3.28 mmol) followed by ethyl chloroformate (0.32 mL, 3.28 mmol). This mixture was stirred at 0° C. for 45 min. In a separate flask, to a suspension of hexane-washed sodium hydride (131 mg of 60% dispersion in mineral oil, 3.28 mmol) in 20 mL of THF was added (1R)-(+)-2,10-camphorsultam (706 mg, 3.28 mmol) as a solution in 5 mL of THF. The mixture was stirred at ambient temperature for 20 min, at which time gas evolution had ceased and a homogeneous solution was obtained. This solution was added to the mixed anhydride solution maintained at 0° C. and the resulting mixture was stirred at 0° C. for 5 min and then was allowed to warm to ambient temperature and was stirred for 1 h. TLC analysis showed the reaction was not complete. In a separate flask an additional portion of the anion of (1R)-(+)-2,10-camphorsultam was prepared as described above (from 130 mg, 0.6 mmol of (1R)-(+)-2,10-camphorsultam and 24 mg of 60% dispersion in mineral oil, 0.6 mmol of sodium hydride). This solution was added to the main reaction mixture and stirring was continued at ambient temperature for 30 min, at which time the reaction was complete. The reaction was quenched with water and diluted with ethyl acetate. The organics were washed with 1N HCl, sat'd aq NaHCO3 and brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, elution with 4:1 hexane/EtOAc) to afford 1.4 g (94%) of the title compound as a foam. LRMS (ESI): 500.2 (M+H)+.

Provenance & Evidence