p-Toluenesulfonic acid → HCID 44200661, compound

Participants

Reaction Steps

To a 500 mL round bottom flask was added 4-chloro-N′-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)benzohydrazide (intermediate 4a) (880 mg, 2.09 mmol, 1.0 equiv.) and anhydrous THF (209 mL). After being flushed with nitrogen, p-toluenesulfonic acid (439 mg, 2.3 mmol, 1.1 equiv.) was added and the solution was stirred for 10 min at room temperature. Then PS-BEMP (2.85 g, 6.27 mmol, 3.0 equiv.) was added. The reaction was stirred at room temperature for 8 h. The contents of the flask were filtered over Celite® in a ground glass fritted funnel and the Celite® was rinsed with several portions of acetone. The solvent was removed in vacuo to yield a yellow solid. The product was purified via flash chromatography (0→50% EtOAc/hexanes, 110 g of silica gel; TLC Rf=0.51, 100% EtOAc, vanillin stain) to provide the desired product as an off-white solid (150 mg, 18%). Other data: 1H NMR (400 MHz, acetone-d6, δ in ppm) 8.01 (d, J=8.79 Hz, 2H), 7.62 (d, J=8.79 Hz, 2H), 7.49 (d, J=8.54 Hz, 1H), 6.86 (d, J=8.54 Hz, 1H), 5.68 (br. d, J=8.31 Hz, 1H), 5.12 (dd, J=3.91, 8.55 Hz, 1H), 4.82 (br. d, J=5.29 Hz, 1H), 4.62 (m, 1H), 2.40 (s, 3H), 1.41 (d, J=6.35 Hz, 3H); LRMS (ESI+) exact mass calcd for C19H16Cl2N4O2 [M]+ 403.26, found 403.4.

Provenance & Evidence