Diiodomethane → HCID 86691268, compound

Participants

Reaction Steps

Under nitrogen, add a solution of trifluoroacetic acid (1.9 mL, 25 mmol) in dichloromethane (12.5 mL) dropwise very slowly to a cooled (ice bath) stirred solution of diethylzinc (1M in heptanes) (25 mL, 25 mmol) in dichloromethane (12.5 mL). After 10 minutes, add a solution of diiodomethane (2.01 mL, 25 mmol) in dichloromethane (12.5 mL). After 10 minutes, add a solution of diethyl (1S,2S,5R,6S)-2-acetamido-4-methylene-bicyclo[3.1.0]hexane-2,6-dicarboxylate (2.46 g, 8.3 mmol) in dichloromethane (12.5 mL). After 60 minutes remove the ice bath and leave the reaction mixture to stir overnight at room temperature. Quench the clear reaction solution by dropwise addition of the reaction mixture to 0.2M aqueous hydrochloric acid (200 mL) under vigorous stirring. After 1 hour separate the dichloromethane layer, wash with brine, dry over magnesium sulfate, filter and concentrate in vacuum to yield the required product contaminated with unreacted starting material (4.4 g). Purify by flash chromatography eluting with ethyl acetate:cyclohexane (50:50 to 100:0) to give a colorless oil (3.1 g). Purify by SFC(RT=2.48 minutes (UV, 200 nm); HPLC Column: AD-H 30 mm×250 mm 5 μm; CO2 gradient: 5% iso-propyl alcohol w/0.2% dimethylethylamine for 0.5 minutes, then 5%-27% in 2.2 minutes. Column temperature: 35° C.; pressure: 100000 kPa; flow rate: 210 mL/minute) to yield unreacted diethyl (1S,2S,5R,6S)-2-acetamido-4-methylene-bicyclo[3.1.0]hexane-2,6-dicarboxylate. (580 mg, 2.0 mmol) and title compound (1.82 g, 5.9 mmol). MS (m/z): 310 (M+1), 332 (M+23).

Provenance & Evidence