Methyl iodide → (2S,3S,4R)-tert-butyl 3-(3-chloro-4-methoxyphenyl)-2,4-dimethyl-5-oxopyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of (2S,3S)-tert-butyl 3-(3-chloro-4-methoxyphenyl)-2-methyl-5-oxopyrrolidine-1-carboxylate (intermediate J1, 0.85 g, 2.5 mmol) in THF (20 mL) was added LiHMDS (2.5 mL, 2.5 mmol) at −78° C. After 30 mins, MeI (0.187 mL, 3.00 mmol) was added. The reaction mixture was stirred at −78° C. for 1.5 hr. It was warmed up to 0° C. for 30 min and then warmed up to RT for 30 min. The reaction mixture was quenched with 2 mL of AcOH and 100 mL of NH4Cl. The product was extracted with EtOAc (3×100 mL). The organic layer was washed with brine (100 mL), dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography, eluted with 30% EtOAc/Hexane to give (2S,3S,4R)-tert-butyl 3-(3-chloro-4-methoxyphenyl)-2,4-dimethyl-5-oxopyrrolidine-1-carboxylate (intermediate J2, 0.55 g, yield of 62%) as off-white solid. 1H NMR (500 MHz, CDCl3): δ 7.29 (s, 1H), 7.14 (d, 1H), 6.95 (d, 1H), 3.93 (s, 3H), 3.91 (m, 1H), 2.58 (m, 1H), 2.40 (m, 1H), 1.59 (s, 9H), 1.38 (d, 3H), 1.17 (d, 3H).

Provenance & Evidence