Methanol → HCID 56598014, compound

Participants

Reaction Steps

A 100 mL round bottom was charged with 4-((1R,2S)-2-(tert-butyldimethylsilyloxy)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)propylamino-2-chloro-3-propylbenzonitrile (intermediate 1119-D) (0.344 g, 0.64 mmole) and methanol (10 mL) at room temperature. Ammonium fluoride (0.119 g, 3.20 mmol) was then added in one portion and the reaction mixture was brought to reflux. The reaction stirred at reflux for 65 h before being cooled to room temperature. To the resulting reaction mixture was added water (50 mL), TBME (30 mL), EtOAc (50 mL) and more water (40 mL). The biphasic mixture was separated and the aqueous layer was extracted with EtOAc (50 mL). The organic extracts were then combined, washed with water (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to provide a brown solid. The brown solid was then purified by flash chromatography over silica gel [EtOAc-hexanes (50%:50%)→EtOAc-hexanes (100%:0%) as eluent] to provide the title compound with other minor impurities (200.7 mg, 74%). 1H NMR (400 MHz, CDCl3 δ in ppm): 8.07 (d, J=8.0 Hz, 2H), 7.77 (d, J=8.0 Hz, 2H), 7.34 (d, J=8.0 Hz, 1H), 6.60 (d, J=8.0 Hz, 1H), 5.45 (d, J=8.0 Hz, 1H), 4.80 (d, J=2.0, 8.0 Hz, 1H), 4.60 (m, 1H), 2.79 (t, J=8.0 Hz, 2H), 1.64 (sextet, J=8.0 Hz, 2H), 1.46 (d, J=4.0 Hz, 3H), 1.07 (t, J=8.0 Hz, 3H).

Provenance & Evidence