Iodine → (R)-2-chloro-4-(1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxy-2-methylpropylamino)-3-methylbenzonitrile

Participants

Reaction Steps

To a solution of triphenylphosphine (1.70 g, 6.48 mmol) in DCM (50 mL) was added I2 (1.63 g, 6.42 mmol) at 0° C. After all the Iodine was dissolved completely, Et3N (1.8 mL, 12.9 mmol) was added, followed by a solution of (R)—N′-(2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxy-3-methylbutanoyl)-4-cyanobenzohydrazide (1.37 g, 3.22 mmol) in DCM (10 mL) and THF (10 mL). After addition, the reaction mixture was allowed to warm to room temperature and stirred for additional 30 min. The reaction was quenched with saturated aq. sodium thiosulfate (10 mL) and diluted with DCM (100 mL). The organic layer was separated and washed with water, brine and dried over Na2SO4. After the solvent was removed, the residue was purified by flash chromatography to provide the title compound (R)-2-chloro-4-(1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxy-2-methylpropylamino)-3-methylbenzonitrile (1.18 g, 90%). 1H NMR (400 MHz, Acetone-d6, δ in ppm) 8.19 (d, J=8.8 Hz, 2H), 7.97 (d, J=8.8 Hz, 2H), 7.46 (d, J=8.6 Hz, 1H), 6.80 (d, J=8.6 Hz, 1H), 5.71 (d, J=9.0 Hz, 1H), 5.14 (d, J=9.0 Hz, 1H), 4.67 (s, 1H), 2.39 (s, 3H), 1.53 (s, 3H), 1.36 (s, 3H).

Provenance & Evidence