Tetrahydrofuran → HCID 66848275, compound

Participants

Reaction Conditions

Reaction Steps

2-Oxopyrrolidine-1-carboxylic acid t-butyl ester (9.3 g, 50.4 mmol) was dissolved in THF (60 mL, 800 mmol) under nitrogen and was then cooled at −78° C. 2M Lithium diisopropylamide in heptane/THF/ethylbenzene (34 mL) was added over 40 minutes, and the resulting mixture was stirred for 1.5 hours at −78° C. Cyclopentanecarbonyl chloride (6.1 mL, 50 mmol) was dissolved in THF (4.0 mL, 49 mmol) and slowly added dropwise via syringe to the mixture over 30 minutes, then stirred at room temperature overnight. The reaction was quenched with saturated aqueous NH4Cl (50 mL) and the mixture stirred at room temperature for 30 minutes. The mixture was extracted with EtOAc (200 mL). The organic layer was washed with saturated aqueous NaHCO3 (2×75 mL), then saturated aqueous NaCl. The aqueous layers were combined and re-extracted with EtOAc (75 mL). The organic layers were combined, dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was then placed on high vacuum for 10 minutes to yield a crude oil. The oil was dissolved in 50% AcOH/H2O and purified by preparative HPLC (10-70% MeCN/H2O; 0.05% TFA; over 80 minutes on a 2″ column at 40 mL/min). The fractions were collected and lyophilized to yield 3-cyclopentanecarbonyl-2-oxopyrrolidine-1-carboxylic acid t-butyl ester (6 g) as a yellow solid. MS m/z: [M+H]+ calcd for C15H23NO4, 281.3; found 282.2.

Provenance & Evidence