Phthalimide → (3S)-tert-butyl 3-((3-chloro-4-fluorophenyl)(1,3-dioxoisoindolin-2-yl)methyl)pyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 69a/69b (364.3 mg, 1.105 mmol) in THF (5.5 mL, 0.2 M) under nitrogen was added phthalimide (178.8 mg, 1.215 mmol) and PPh3 (376.7 mg, 1.436 mmol). The reaction was cooled to 0° C. and diethyl azodicarboxylate (654.0 μL, 1.436 mmol) was added dropwise via syringe. The reaction was allowed to warm to RT and stirred for 16 h. The reaction was concentrated to dryness by rotovap, diluted to 30 mL with EtOAc and washed with water (2×30 mL) and brine (1×30 mL). The organics were isolated, dried (Na2SO4), filtered and concentrated. The crude product was purified by SiO2 chromatography eluting with a hexanes/acetone gradient (5 to 70% acetone) to afford 212 mg (42%) of 71a/71b as a clear oil containing approximately a 1:1 mixture of diastereomers.

Provenance & Evidence