Methyl iodide → (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(5'-chloro-2'-vinylbiphenyl-4-yl)-4-methoxypyrrolidine-1,2-dicarboxylate

Participants

Reaction Steps

NaH (60% in oil) (106 mg, 2.65 mmol) was added to a solution of (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(5′-chloro-2′-vinylbiphenyl-4-yl)-4-hydroxypyrrolidine-1,2-dicarboxylate (740 mg, 1.474 mmol) and methyl iodide (0.166 mL, 2.65 mmol) at 0° C. in DMF and stirred at this temperature and allowed to warm up to r.t. overnight. The reaction was then quenched with saturated NH4Cl solution and ether. The ether layer was washed with brine, dried, filtered and evaporated to give crude material. The crude material was purified by flash chromatography on the Biotage (5-40% EtOAc in hexanes) to give semi purified product (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(5′-chloro-2′-vinylbiphenyl-4-yl)-4-methoxypyrrolidine-1,2-dicarboxylate (333 mg, 0.645 mmol, 44% yield) as a clear oil. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 0.04 (s, 9H) 1.01-1.06 (m, 2H) 2.52 (dd, J=13.12, 8.85 Hz, 1H) 2.78-2.87 (m, 1H) 2.97 (d, J=5.19 Hz, 3H) 3.65 (s, 1H) 3.67-3.75 (m, 3H) 3.77 (d, J=8.85 Hz, 3H) 3.96-4.08 (m, 1H) 5.21 (d, J=10.99 Hz, 1H) 5.68 (d, J=17.40 Hz, 1H) 6.59 (ddd, J=17.47, 11.06, 2.29 Hz, 1H) 7.26 (d, J=2.14 Hz, 1H) 7.29-7.35 (m, 3H) 7.35-7.40 (m, 2H) 7.56 (d, J=8.24 Hz, 1H).

Provenance & Evidence