Methane → (2R,4S)-4-fluoropyrrolidine-2-carboxylic acid

The crude trans-4-fluoro-D-proline (146.55 g) was dissolved in 200 mL of boiling water, 2.0 g of charcoal were added, and the mixture was filtered while hot through Celite®, rinsing with 90 mL of hot water. The solution was heated to reflux, 580 mL of ethanol was added slowly at reflux and the mixture was allowed to cool to room temperature overnight. The crystalline precipitate was then filtered, washed with 2:1 ethanol-water (total 100 mL), then with ethanol, and dried to afford 91.47 g of trans-4-fluoro-D-proline as off-white crystals melting at 258-260° C. with decomposition. 1H NMR (D2O): δ1.9-2.2 (m, 1H), 2.45-2.65 (m, 1H), 3.3-3.6 (m, 2H), 4.20 (dd, 1H), 5.33 (d, J=52 Hz, 1H). Additional crops could be collected by concentration of the filtrates, but they would be of lesser purity.

1. filtrationthe mixture was filtered while hot through Celite®
2. washrinsing with 90 mL of hot water
3. temperatureThe solution was heated
4. temperatureto reflux
5. addition580 mL of ethanol was added slowly
6. temperatureat reflux
7. filtrationThe crystalline precipitate was then filtered
8. washwashed with 2:1 ethanol-water (total 100 mL)
9. dry with materialwith ethanol, and dried

ORD record

ord-0760c663062249f5a13aa1abdc15ded9

Source dataset

uspto-grants-2003_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06664400B2