1,2-Dichloroethane → HCID 69585353, compound

Participants

Reaction Steps

A mixture of 4-amino-5-ethoxy-5H-furan-2-one (0.13 g, 0.75 mmol), (S)-pyrrolidine-1,2-dicarboxylic acid-1-tert-butyl ester (0.16 g, 0.75 mmol) and several crystals of Congo Red indicator in ethanol (5 mL) was treated with sodium cyanoborohydride (0.06 g, 0.90 mmol), followed by dropwise addition of 4M HCl in dioxane to attain and maintain a blueish color (˜pH3). The reaction was stirred 2 h, was filtered (Celite) and was evaporated. The residue was dissolved in dichloromethane (5 mL), was treated with di-isopropylethylamine (0.52 mL, 3.0 mmol), EDC (0.18 g, 0.94 mmol), and HOBT (0.13 g, 0.94 mmol) and was stirred at room temperature under nitrogen for 20 h. The reaction was diluted with ethyl acetate, was washed with 10% sodium bisulfate, saturated sodium bicarbonate, and brine, was dried over sodium sulfate, and was evaporated. Purification by flash chromatography (SiO2) eluted with 1:1 ethyl acetate:hexanes provided a 4:1 mixture (by 1H-NMR) of (R)-2-[(2R,3S)-2-ethoxy-5-oxo-tetrahydrofuran -3-ylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester and (R)-2-[(2S,3S)-2-ethoxy-5-oxo-tetrahydrofuran-3-ylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.06 g, 23% yield) as a colorless oil. 1H-NMR (500 MHz, CDCl3) δ 7.60 (br, 0.15H), 7.44 (br s, 0.5H), 6.51 (0.35H), 5.38 (d, J=5.3 Hz, 0.8H), 5.29 (s, 0.2H), 4.65 (br m, 0.8H), 4.1-4.3 (br m, 1.2H), 3.84 (m, 0.8H), 3.78 (m, 0.2H), 3.59 (m, 1H), 3.25-3.45 (br m, 2H), 2.95 (dd, J=17.6, 7.1 Hz, 0.2H), 2.78 (br m, 0.8H), 2.34 (dd, J=17.2, 10.4 Hz, 0.8H), 1.9-2.3 (br 1.7H), 1.83 (br s, 2.5H), 1.39 (s, 9H), 1.19 (m, 3H) ppm.

Provenance & Evidence