Tempo → 2,5-Difluoro-4-(3-oxoazetidin-1-yl)-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide

To a solution of 2,5-difluoro-4-(3-hydroxyazetidin-1-yl)-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide (7.57 g, 23.3 mmol) in methylene chloride (93 mL) was added iodobenzene diacetate (9.40 g, 29.2 mmol) and 2,2,6,6-tetramethyl-1-piperidinyloxy free radical (1.82 g, 11.7 mmol) (TEMPO) at room temperature. The reaction mixture was stirred at room temperature overnight. The mixture was diluted with EtOAc (100 mL), washed with 0.5N NaHCO3 (2×80 mL), 20% brine (100 mL) and water (100 mL). The aqueous layers were extracted with ethyl acetate (75 mL). The organic extracts were combined, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluting with 0% to 5% ethyl acetate in methylene chloride to afford the crude product which was recrystallized from MTBE (50 mL) and heptane (100 mL) to give the desired product (5.44 g, 72%) as colorless solid. 1H NMR (300 MHz, DMSO-d6) δ 8.52 (d, J=8.0 Hz, 1H), 7.36 (dd, J=12.5, 6.5 Hz, 1H), 6.63 (dd, J=12.1, 7.6 Hz, 1H), 4.90 (d, J=2.1 Hz, 4H), 4.86-4.68 (m, 1H), 1.31 (d, J=7.1 Hz, 3H) ppm. LCMS cacld. for C13H12F5N2O2 (M+1)+: m/z=323.1. Found: 323.0.

1. washwashed with 0.5N NaHCO3 (2×80 mL), 20% brine (100 mL) and water (100 mL)
2. extractionThe aqueous layers were extracted with ethyl acetate (75 mL)
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by flash chromatography on a silica gel column
7. washeluting with 0% to 5% ethyl acetate in methylene chloride
8. customto afford the crude product which
9. customwas recrystallized from MTBE (50 mL) and heptane (100 mL)

ORD record

ord-0a09a33ec84e4aad9b4964f6c8c9e6be

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09382231B2