D-Proline, 4,4-difluoro-, methyl ester → methyl 4-fluoro-1H-pyrrole-2-carboxylate

Temperature

70 °C

To solution of (R)-methyl 4,4-difluoropyrrolidine-2-carboxylate (2.00 g, 12.11 mmol) in THF (40 mL) was added manganese dioxide (8.42 g, 97 mmol) and the resulting mixture was heated at reflux (oil bath temp ˜70° C.) for 3 h. After cooling to rt, the reaction mixture was filtered through a pad of Celite, rinsed with additional THF (20 mL×4), and DCM (40 mL×4) and the resulting filtrate was concentrated under vacuum to afford a dark brown oil as the crude product which was purified via flash silica gel chromatography (eluent: CH2Cl2/MeOH, 0-10%) to afford 0.98 g (56%) of the title compound as a white solid. HPLC (condition B): retention time=1.71 min. LCMS (condition B): m/z 144 +ve. 1H NMR (400 MHz, MeOD) δ ppm 6.81 (1 H, dd, J=3.63, 1.87 Hz), 6.59 (1 H, d, J=1.32 Hz), 3.86 (3 H, s).

1. temperaturethe resulting mixture was heated
2. temperatureAfter cooling to rt
3. filtrationthe reaction mixture was filtered through a pad of Celite
4. washrinsed with additional THF (20 mL×4), and DCM (40 mL×4)
5. concentrationthe resulting filtrate was concentrated under vacuum
6. customto afford a dark brown oil as the crude product which
7. customwas purified via flash silica gel chromatography (eluent: CH2Cl2/MeOH, 0-10%)

ORD record

ord-c699b66dfb9e4dbf840a93401d0cce62

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09221826B2